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• W2002135246 abstract "Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell–cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus. Pemphigus refers to a group of autoimmune blistering skin diseases, mainly identified as pemphigus vulgaris and pemphigus foliaceus, both characterized by the presence of autoantibodies against keratinocyte adhesion molecules, leading to loss of cell–cell adhesion with consequent blister formation. Pemphigus vulgaris is reported to be associated with human leukocyte antigen DR4 and/or DR6 whereas no data are available on pemphigus foliaceus, except for the endemic Brazilian form (fogo selvagem), which is reported to be associated with DR1 and DR4. We here report human leukocyte antigen molecular typing on a total of 87 patients, 61 with pemphigus vulgaris and 26 with pemphigus foliaceus, versus 128 healthy matched controls. Generic typing showed an increase of DRB1*04 and DRB1*14 and a decrease of DRB1*07 in both pemphigus vulgaris and pemphigus foliaceus patients. Molecular subtyping of DR4+ and DR14+ subjects showed a highly significant association between the DRB1*1401 and both pemphigus vulgaris (p < 0.0001) and pemphigus foliaceus patients (p < 0.0001) together with a significant increase of the linked DQB1*0503 (pemphigus vulgaris p < 0.0001; pemphigus foliaceus p < 0.0001). Moreover, whereas the association between DRB1*0402 and pemphigus vulgaris (p < 0.0001) has been confirmed, no significant association between a specific allele of the DR4 group and pemphigus foliaceus, has been found. Therefore, at least in Italian patients, pemphigus vulgaris and pemphigus foliaceus share DRB1*1401 and DQB1*0503, as susceptible human leukocyte antigen alleles, whereas DRB1*0402 is only found associated with pemphigus vulgaris. The observation that both diseases, pemphigus vulgaris and pemphigus foliaceus, carry the same susceptible human leukocyte antigen alleles has been interpreted as a common genetic background predisposing to pemphigus as, like in other autoimmune disorders, it is not sufficient to explain the onset of the disease on the basis of the sole aforementioned alleles. Other linked genes and/or environmental factors should play a facilitating role in the outbreak of pemphigus, either pemphigus vulgaris or pemphigus foliaceus. human leukocyte antigen pemphigus vulgaris pemphigus foliaceus polymerase chain reaction–sequence-specific primers desmoglein 1 desmoglein 3 The intraepidermal blistering autoimmune disease known as pemphigus can be divided into two main forms, vulgaris (PV) and foliaceus (PF), according to clinical, histologic, and immunologic features (Nousari and Anhalt, 1995Nousari H.C. Anhalt G.J. Bullous skin diseases.Curr Opin Immunol. 1995; 7: 844-852Crossref PubMed Scopus (28) Google Scholar). Both forms are characterized by loss of epidermal cell–cell cohesion leading to acantholysis and by the presence of pathogenic IgG autoantibodies directed against cellular adhesion molecules desmoglein 3 (Dsg3) and desmoglein 1 (Dsg1) (Stanley, 1989Stanley J.R. Pemphigus and pemphigoid as paradigms of organ-specific, autoantibody-mediated diseases.J Clin Invest. 1989; 83: 1443-1448Crossref PubMed Scopus (171) Google Scholar;Amagai et al., 1991Amagai M. Klaus-Kovtun V. Stanley J.R. Autoantibodies against a novel epithelial cadherin in pemphigus vulgaris, a disease of cell adhesion.Cell. 1991; 67: 869-877Abstract Full Text PDF PubMed Scopus (827) Google Scholar;Karpati et al., 1994Karpati S. Amagai M. Prussick R. Stanley J.R. Pemphigus vulgaris antigen is a desmosomal desmoglein.Dermatol. 1994; 189: 24-26Crossref Scopus (12) Google Scholar), which have been identified as PV and PF antigens, respectively (Stanley et al., 1984Stanley J.R. Koulu L. Thivolet C. Distinction between epidermal antigens binding pemphigus vulgaris and pemphigus foliaceus autoantibodies.J Clin Invest. 1984; 74: 313-320Crossref PubMed Scopus (204) Google Scholar;Eyre and Stanley, 1988Eyre R.W. Stanley J.R. Identification of pemphigus vulgaris antigen extracted from normal human epidermis and comparison with pemphigus foliaceus antigen.J Clin Invest. 1988; 81: 807-812Crossref PubMed Scopus (187) Google Scholar). Genetic predisposition, found in several autoimmune diseases, has been reported also for pemphigus, and the association between human leukocyte antigen (HLA) class II genes and PV is well documented (Scharf et al., 1988Scharf S.J. Friedmann A. Brautbar C. et al.HLA class II allelic variation and susceptibility to pemphigus vulgaris.Proc Natl Acad Sci USA. 1988; 85: 3504-3508Crossref PubMed Scopus (177) Google Scholar;Ahmed et al., 1990Ahmed A.R. Yunis E.J. Khatri K. et al.Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris.Proc Natl Acad Sci USA. 1990; 87: 7658-7662Crossref PubMed Scopus (180) Google Scholar, Ahmed et al., 1991Ahmed A.R. Wagner R. Khatri K. et al.Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.Proc Natl Acad Sci USA. 1991; 88: 5056-5060Crossref PubMed Scopus (138) Google Scholar). Moreover, molecular analysis of the HLA D region (DP, DQ, DR) has revealed that PV–HLA class II gene association is more stringent because of its correlation with particular allele specificities. DRB1*0402 and/or DQB1*0503 in DR14 positive patients, are the most frequent allele specificities reported in association with PV in several ethnic groups (Niizeki et al., 1994Niizeki H. Inoko N. Mizuki N. et al.HLA-DQA1-DQB1 and DRB1genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method.Tissue Antigens. 1994; 44: 248-251Crossref PubMed Scopus (49) Google Scholar;Carcassi et al., 1996Carcassi C. Cottoni F. Floris L. et al.HLA haplotypes and class II molecular alleles in Sardinian and Italian patients with pemphigus vulgaris.Tissue Antigens. 1996; 48: 662-667Crossref PubMed Scopus (49) Google Scholar;Delgado et al., 1996aDelgado J.C. Yunis D.E. Bozon M.V. et al.MHC class II alleles and haplotype in patients with pemphigus vulgaris from India.Tissue Antigens. 1996; 48: 668-672Crossref Scopus (51) Google Scholar;Lombardi et al., 1996Lombardi M.L. Mercuro O. Tecame G. et al.Molecular analysis of HLA DRB1 and DQB1 in Italian patients with pemphigus vulgaris.Tissue Antigens. 1996; 47: 228-230Crossref PubMed Scopus (41) Google Scholar). No data are available on PF, except for the endemic Brazilian form, fogo selvagem, which has been reported to be associated with DR1 and DR4 (Petzl-Erler and Santamaria, 1989Petzl-Erler M.L. Santamaria J. Are HLA class II genes controlling susceptibility and resistance to Brazilian pemphigus foliaceus (fogo selvagem) ?.Tissue Antigens. 1989; 33: 408-414Crossref PubMed Scopus (58) Google Scholar;Moraes et al., 1991Moraes J.R. Moraes E.M. Fernandez-Vina M. et al.HLA antigens and risk for development of pemphigus foliaceus (fogo selvagem) in endemic areas of Brazil.Tissue Antigens. 1991; 33: 388-391Google Scholar;Cerna et al., 1993Cerna M. Fernandez-Vina M. Friedman H. Moraes J.R. Moraes M.E. Diaz L. Stastny P. Genetic markers for susceptibility to endemic Brazilian pemphigus foliaceus (fogo selvagem) in Xavante indians.Tissue Antigens. 1993; 47: 138-140Crossref Scopus (30) Google Scholar;Moraes et al., 1997Moraes M.E. Fernandez-Vina M. Lazaro A. et al.An epitope in the third hypervariable region of the DRB1 gene is involved in the susceptibility to endemic pemphigus foliaceus (fogo selvagem) in three different Brazilian population.Tissue Antigens. 1997; 49: 35-40Crossref PubMed Scopus (99) Google Scholar). We previously reported a significant association between PV and the alleles DRB1*0402, DRB1*1401, and DQB1*0503 in Italian Caucasian, non-Jewish patients with a clear predominance of DR14 compared with DR4 (Lombardi et al., 1996Lombardi M.L. Mercuro O. Tecame G. et al.Molecular analysis of HLA DRB1 and DQB1 in Italian patients with pemphigus vulgaris.Tissue Antigens. 1996; 47: 228-230Crossref PubMed Scopus (41) Google Scholar). We here report for the first time the molecular analysis of DRB1 and DQB1 alleles in Italian Caucasian, non-Jewish patients affected by PF compared with PV patients and healthy controls of the same geographic area. All patients and controls enrolled in the study were of non-Jewish, strict Italian origin, from the southern regions of the country. The diagnosis of PV or PF was based on clinical, histologic, and immunologic data. In particular, histopathologic examination of a skin lesion revealed suprabasal or subcorneal acantholysis in any PV or PF specimen, respectively, and direct immunofluorescence studies detected intercellular deposition of both IgG and C3 in the perilesional epidermis of all patients. Homozygous B lymphoblastoid cell lines from the 10th International Histocompatibility Workshop were used as standard in HLA molecular typing. Genomic DNA was prepared from peripheral blood leukocytes by phenol extraction according to standard procedures. Molecular analysis of DRB1 and DQB1 was carried out, as previously described (Lombardi et al., 1998Lombardi M.L. Mercuro O. Pirozzi G. Ionna F. Mozzillo N. Manzo C. Molecular analysis of HLA DRB1 and DQB1 polymorphism in Italian melanoma patients.J Immunotherapy. 1998; 21: 435-439Crossref PubMed Scopus (15) Google Scholar), either by the sequence-specific oligonucleotide hybridization technique of polymerase chain reaction (PCR) -amplified DNA (Kimura and Sasazuki, 1992Kimura A. Sasazuki T. Tsuji K. Aizawa M. Sasazuki T. Eleventh International Histocompatibility Workshop Reference Protocol for the HLA DNA Typing Technique. Oxford University Press, Oxford1992: 397-419Google Scholar) or by PCR–sequence-specific primers (SSP) (Olerup and Zetterquist, 1992Olerup O. Zetterquist H. HLA-DR typing by PCR amplification with sequence specific primers (PCR–SSP) in 2 hours. An alternative to serological DR typing in clinical practice including donor-recipient matching in cadaveric transplantation.Tissue Antigens. 1992; 39: 225-235Crossref PubMed Scopus (1704) Google Scholar;Olerup et al., 1993Olerup O. Aldener A. Fogdell A. HLA-DQB1 and DQA1 typing by PCR amplification with sequence specific primers (PCR–SSP) in 2 hours.Tissue Antigens. 1993; 41: 119-134Crossref PubMed Scopus (565) Google Scholar). Commercial kits (Dynal, Skøyen, Norway) for PCR–SSP low and high resolution of DRB1 and DQB1 were used according to the manufacturer’s instructions. Amplification was carried out by using Taq-polymerase-Gold (Perkin Elmer, Foster City, CA). Molecular subtyping of DRB1*04 and DRB1*14 positive patients and controls was performed using a PCR–SSP method able to discriminate among the 25 different allele specificities of the DRB1*04 and the 30 of the DRB1*14 group. DQB1 typing of controls was also performed by the PCR–sequence-specific oligonucleotide method according to the protocol of the 11th International Histocompatibility Workshop (Kimura and Sasazuki, 1992Kimura A. Sasazuki T. Tsuji K. Aizawa M. Sasazuki T. Eleventh International Histocompatibility Workshop Reference Protocol for the HLA DNA Typing Technique. Oxford University Press, Oxford1992: 397-419Google Scholar). Locus-specific primers were used for the DQB1 amplification and dot-blotted filters with amplified DNA were hybridized with γ-32P-adenosine triphosphate-labeled probes. Alleles were assigned according to the nomenclature for factors of the HLA system (Bodmer et al., 1997Bodmer J.G. Marsh G.E. Albert E.D. et al.Nomenclature for factors of the HLA system.Tissue Antigens. 1997; 49: 297-320Crossref PubMed Scopus (299) Google Scholar). p-values were calculated by the Fisher’s two-tailed exact test. The corrected p-values were obtained by multiplying the p-value for the number of measured alleles in each locus tested. Molecular typing, using a low resolution PCR–SSP method, has been carried out on 61 PV and only on 26 PF patients because of the very low incidence of PF with respect to PV in the Italian population. Data have been compared with 128 healthy controls. Results, reported in Table 1, showed a highly significant increase of DRB1*14 in both groups of patients reaching 62.2% in PV (p < 0.0001) and 57.6% in PF patients (p < 0.0001) compared with 12.5% found in controls. Moreover, an increase of DRB1*04, which reaches 34.4% in PV (p = 0.04) and 34.6% in PF patients (p = 0.33) versus 15.6% found in controls, can be noted. Therefore, as previously reported for PV, DR14 seems to be the most represented specificity also in PF patients.Table 1DRB1 alleles frequency in PV and PF patients compared with controlsPV patients (61)PF patients (26)DRB1*Controls (128) %%paCorrected p values.%p0111.78.1–11.5–159.38.1–3.8–167.84.9–11.5–0313.38.1–––0415.634.4= 0.0434.6= 0.331154.637.7–38.4–120.8––––1315.68.1–7.6–1412.562.2 <0.0001bp = 5.5 × 10–11.57.6<0.0001cp = 3.0 × 10–5.0727.36.5<0.017.6= 0.26083.113.1–15.3–100.8––––a Corrected p values.b p = 5.5 × 10–11.c p = 3.0 × 10–5. Open table in a new tab The frequency of other DRB1 alleles showed a nonsignificant increase of DRB1*08 and a decrease of DRB1*07, the latter present only in 6.5% of PV (p < 0.01) and in 7.6% of PF patients (p = 0.26) compared with the value of 27.3% found in the normal population. It should be noted that, in both DR4 and DR14 positive patients, 96.6% of PV and 92.2% of PF subjects had an associated antigen, seven of 61 PV and five of 26 PF patients did not carry any associated antigen, and six PV and two PF patients had both the DR4 and the DR14 antigens. As the most significant difference, between patients and controls, was found in the frequency of DRB1*04 and DRB1*14, all the subjects carrying these alleles were subtyped by PCR–SSP high-resolution methods, looking for a more stringent association with a particular allele specificity. An interesting difference between PV and PF patients emerged by comparing the subtyping of DRB1*04+ subjects (Table 2). In fact, DRB1*0402 was found to be present in 20 of 21 DR4+ PV patients and the difference compared with controls was highly significant (p < 0.0001). Only four of nine DR4+ PF patients, on the contrary, showed the DRB1*0402 and the difference was not statistically significant (p = 0.70). The remaining DR4+ PF patients showed a wide distribution of different allele specificities as found in the DR4+ control group. Uniformity of results between PV and PF patients was, on the contrary, found by analyzing the high-resolution subtyping of DR14+ subjects (Table 3), which showed a highly significant increase of DRB1*1401 both in PV (p < 0.0001) and in PF patients (p < 0.005). Moreover, a significant increase of DRB1*1404 was found in PV patients (p < 0.01), which should be confirmed on a larger number of subjects because of the rare presence of this allele in the normal population.Table 2DRB1 alleles frequency in DR4+ PV and PF patients compared with controlsaNo controls or patients were positive for DRB1*0409–0425. One PV patients was DRB1*0402,0403.PV patients (61)PF patients (26)DRB1*Controls (128) %%pbCorrected p values.%p04014.8––3.8–04023.132.7<0.0001cp = 1.1 × 10–6.15.3=0.7004033.11.6–––04041.61.6–––04051.6––7.6–04070.8––3.8–04080.8––3.8–a No controls or patients were positive for DRB1*0409–0425. One PV patients was DRB1*0402,0403.b Corrected p values.c p = 1.1 × 10–6. Open table in a new tab Table 3DRB1 alleles frequency in DR14+ PV and PF patients compared with controlsaNo controls or patients were positive for DRB1*1408–1430.PV patients (61)PF patients (26)DRB1*%%pbCorrected p values.%p140111.744.2<0.0001cp = 3.5 × 10–5.46.1<0.00514040.816.3<0.0111.5=0.451407–1.6–––a No controls or patients were positive for DRB1*1408–1430.b Corrected p values.c p = 3.5 × 10–5. Open table in a new tab Molecular analysis of DQB1 polymorphism is reported in Table 4. The most striking difference between both groups of patients and controls is the highly significant increase of DQB1*0503 in linkage with DR14. It reaches 62.2% in PV (p < 0.0001) and 57.6% in PF patients (p < 0.0001) with respect to the frequency of 8.5% found in controls. Moreover, also DQB1*0302, in linkage with DR4, is increased in both groups of patients with values of 34.4% in PV (p < 0.005) and 34.6% in PF patients (p = 0.057) compared with the value of 10.9% found in controls. Owing to the strong linkage between DR and DQ loci, all the patients carrying the DRB1*14 had the DQB1*0503, as well as all the patients carrying the DRB1*04 who had the DQB1*0302. Moreover, the decrease of DQB1*02, found in both diseases, is a consequence of the decrease of the linked DRB1*07.Table 4DQB1 alleles frequency in PV and PF patients compared with controlsPV patients (61)PF patients (26)DQB1*Controls (128) %%paCorrected p values.%p0232.814.7= 0.073.8<0.05030157.847.5–46.1–030210.934.4<0.00534.6= 0.05703032.3––3.8–04021.68.1–11.5–050112.53.2–15.3–05029.36.5–11.5–05038.562.2<0.0001bp = 1.8 × 10–12.57.6<0.0001cp = 1.2 × 10–6.06015.41.6–––06025.44.9–3.8–06036.2––––060410.98.1–3.8–a Corrected p values.b p = 1.8 × 10–12.c p = 1.2 × 10–6. Open table in a new tab No association between allelic frequencies and groups of patients, defined by disease location, recurrence, antibody titre, and response to immunosuppressive therapy was found. No significant differences in clinical features were observed in PV or PF patients carrying both DR4 and DR14 alleles. We have only observed that DR4 frequency in PV patients was 2.06 times higher in women (44.7%) than in men (21.7%). Several studies reported different HLA allele specificities associated with PV in different ethnic groups (Scharf et al., 1988Scharf S.J. Friedmann A. Brautbar C. et al.HLA class II allelic variation and susceptibility to pemphigus vulgaris.Proc Natl Acad Sci USA. 1988; 85: 3504-3508Crossref PubMed Scopus (177) Google Scholar;Ahmed et al., 1990Ahmed A.R. Yunis E.J. Khatri K. et al.Major histocompatibility complex haplotype studies in Ashkenazi Jewish patients with pemphigus vulgaris.Proc Natl Acad Sci USA. 1990; 87: 7658-7662Crossref PubMed Scopus (180) Google Scholar, Ahmed et al., 1991Ahmed A.R. Wagner R. Khatri K. et al.Major histocompatibility complex haplotypes and class II genes in non-Jewish patients with pemphigus vulgaris.Proc Natl Acad Sci USA. 1991; 88: 5056-5060Crossref PubMed Scopus (138) Google Scholar;Niizeki et al., 1994Niizeki H. Inoko N. Mizuki N. et al.HLA-DQA1-DQB1 and DRB1genotyping in Japanese pemphigus vulgaris patients by the PCR-RFLP method.Tissue Antigens. 1994; 44: 248-251Crossref PubMed Scopus (49) Google Scholar;Carcassi et al., 1996Carcassi C. Cottoni F. Floris L. et al.HLA haplotypes and class II molecular alleles in Sardinian and Italian patients with pemphigus vulgaris.Tissue Antigens. 1996; 48: 662-667Crossref PubMed Scopus (49) Google Scholar;Lombardi et al., 1996Lombardi M.L. Mercuro O. Tecame G. et al.Molecular analysis of HLA DRB1 and DQB1 in Italian patients with pemphigus vulgaris.Tissue Antigens. 1996; 47: 228-230Crossref PubMed Scopus (41) Google Scholar) whereas few data are available on HLA association and PF except for the Brazilian form where DRB1*0102 (Moraes et al., 1991Moraes J.R. Moraes E.M. Fernandez-Vina M. et al.HLA antigens and risk for development of pemphigus foliaceus (fogo selvagem) in endemic areas of Brazil.Tissue Antigens. 1991; 33: 388-391Google Scholar) and DRB1*01, 0404, 1402, and 1406 (Cerna et al., 1993Cerna M. Fernandez-Vina M. Friedman H. Moraes J.R. Moraes M.E. Diaz L. Stastny P. Genetic markers for susceptibility to endemic Brazilian pemphigus foliaceus (fogo selvagem) in Xavante indians.Tissue Antigens. 1993; 47: 138-140Crossref Scopus (30) Google Scholar;Moraes et al., 1997Moraes M.E. Fernandez-Vina M. Lazaro A. et al.An epitope in the third hypervariable region of the DRB1 gene is involved in the susceptibility to endemic pemphigus foliaceus (fogo selvagem) in three different Brazilian population.Tissue Antigens. 1997; 49: 35-40Crossref PubMed Scopus (99) Google Scholar) have been found in different racial groups. We here report, for the first time, the molecular analysis of DRB1 and DQB1 polymorphism in Italian patients affected by PF comparing the data with those of PV patients and controls of the same geographic area. The main result of the investigation has been the demonstration of a highly significant association between PF and the alleles DRB1*1401,and DQB1*0503, the same found also for PV. A decrease of DR7 together with the linked DQB1*02 and an increase of DRB1*04 in both groups has been also noted, and whereas molecular subtyping of DR4+ patients showed a clear association between DRB1*0402 and PV, no association between any allele of the DR4 group and PF has been detected. A brief communication on French patients confirms the above observation reporting an increase of DR4 in both PV and PF, but DRB1*0402 was only found in PV patients (Le Cleach et al., 1997Le Cleach L. Loiseau P. Lepage V. et al.HLA de class II et susceptibilitè au Pemphigus vulgaire et superficiel en France.Ann Dermatol Venereol. 1997; 124: S30Google Scholar). Moreover alleles of HLA DR4 (DRB1*0403,*0406) and DR14 groups (DRB1*1401,*1405, 1406) have been found both in PF and PV Japanese patients (Miyagawa et al., 1997Miyagawa S. Higashimine I. Iida T. Yamashina Y. Fukumoto T. Shirai T. HLA DRB1*04 and DRB1*14 alleles are associated with susceptibility to pemphigus among Japanese.J Invest Dermatol. 1997; 109: 615-618Abstract Full Text PDF PubMed Scopus (65) Google Scholar). A further consideration arising from the results is that DR4 and the linked DRB1*0302 are both equally increased as the latter was present in any patient carrying DR4 (Begovich et al., 1992Begovich A.B. McClure G.R. Suraj V.C. et al.Polymorphism, recombination, and linkage disequilibrium within the HLA class II region.J Immunol. 1992; 148: 249-258PubMed Google Scholar). It is difficult, of course, to assign a primary association with the DR or with the DQ locus because the significant increase of DQB1*0302 could be only due to linkage disequilibrium. Only an analysis on a larger number of PF patients comparing data of different ethnic groups could give an insight to the question. Moreover, to clarify better the role of DR and DQ alleles, functional studies on HLA restricted T cell response should be extended also to PF because when applied to PV, the T cell response against peptides derived from Dsg3 appeared to be only restricted to HLA-DR and not to DQ or DP (Lin et al., 1997Lin M.S. Swartz S.J. Lopez A. et al.Development and characterization of Desmoglein-3 specific T cell from patients with pemphigus vulgaris.J Clin Invest. 1997; 99: 31-40Crossref PubMed Scopus (144) Google Scholar). The observation that patients with both diseases, PV and PF, carry the same associated alleles (DRB1*1401, DQB1*0503) deserves further consideration. It is possible that the sharing of significant amino acid sequence homologies between the autoantigens Dsg3 and Dsg1 (Amagai, 1995Amagai M. Adhesion molecules. I. Keratinocyte–keratinocyte interaction; cadherins and pemphigus.J Invest Dermatol. 1995; 104: 146-152Crossref PubMed Scopus (142) Google Scholar) can give rise, as a consequence, to a generation of peptides so similar as to bind the same HLA allele. This hypothesis is supported by the observation that peptides derived from Dsg3 can be selectively presented to T cell clones by antigen-presenting cells that carry the DRB1*0402 or the DRB1*1401 (Wucherpfennig et al., 1995Wucherpfennig K.W. Yu B. Bhol K. et al.Structural basis for major histocompatibility complex (MHC) -linked susceptibility to autoimmunity: Charged residues of a single MHC pocket confer selective presentation of self-peptides in pemphigus vulgaris.Proc Natl Acad Sci USA. 1995; 92: 11935-11939Crossref PubMed Scopus (197) Google Scholar;Lin et al., 1997Lin M.S. Swartz S.J. Lopez A. et al.Development and characterization of Desmoglein-3 specific T cell from patients with pemphigus vulgaris.J Clin Invest. 1997; 99: 31-40Crossref PubMed Scopus (144) Google Scholar) and, more interestingly, that T cells from some PF patients respond to the same Dsg3 derived peptide (Lin et al., 1997Lin M.S. Swartz S.J. Lopez A. et al.Development and characterization of Desmoglein-3 specific T cell from patients with pemphigus vulgaris.J Clin Invest. 1997; 99: 31-40Crossref PubMed Scopus (144) Google Scholar). Furthermore, the observation that patients with both forms of pemphigus, PV and PF, carry the same susceptible HLA alleles can only be interpreted as a common genetic background predisposing to pemphigus. Other different factors could then determine both, the onset and the clinical form of the disease. A similar sharing of HLA alleles in different clinical forms of an immune blistering disorder has already been reported between DQB1*0301 and three different variants of bullous pemphigoid (Delgado et al., 1996bDelgado J.C. Turbay D. Yunis E.J. et al.A common major histocompatibility complex class II allele HLA-DQB1*0301 is present in clinical variant of pemphigoid.Proc Natl Acad Sci USA. 1996; 93: 8569-8571Crossref PubMed Scopus (161) Google Scholar). It is evident, therefore, that genetic predisposition is not able, by itself, to explain the pathogenesis of these diseases. A demonstration of this may be the finding, in some pemphigus patients’ sera, of autoantibodies that recognize both PV and PF antigens in the presence of clinical manifestations typical of only one form (Hashimoto et al., 1990Hashimoto T. Ogawa M.M. Konohana A. Nishikawa T. Detection of pemphigus vulgaris and pemphigus foliaceus antigens by immunoblot analysis using different antigen sources.J Invest Dermatol. 1990; 94: 327-331Abstract Full Text PDF PubMed Google Scholar;Amagai et al., 1996Amagai M. Koch P.J. Nishikawa T. Stanley J.R. Pemphigus vulgaris antigen (Desmoglein 3) is localized in the lower epidermis, the site of blister formation in patients.J Invest Dermatol. 1996; 106: 351-355Crossref PubMed Scopus (181) Google Scholar). Moreover, in the serum of healthy relatives of PV patients low levels of non-pathogenic, specific autoantibodies can be detected (Mohimen et al., 1993Mohimen A. Narula M. Ruocco V. Pisani M. Ahmed A.R. Presence of the autoantibody in healthy relatives of Italian patients with pemphigus vulgaris.Arch Dermatol Res. 1993; 285: 176-177Crossref PubMed Scopus (23) Google Scholar;Brandsen et al., 1997Brandsen R. Frusic Zlotkin M. Lyubimov H. et al.Circulating pemphigus IgG in families of patients with pemphigus. Comparison of indirect immunofluorescence, direct immunofluorescence and immunoblotting.J Am Acad Dermatol. 1997; 36: 44-52Abstract Full Text Full Text PDF PubMed Scopus (54) Google Scholar), and these autoantibodies have been correlated with the presence, in the family group, of DR4 or DR6 antigens, which was the same found in PV patients (Ahmed et al., 1993Ahmed A.R. Mohimen A. Yunis E.J. et al.Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients.J Exp Med. 1993; 177: 419-424Crossref PubMed Scopus (77) Google Scholar). Disease can occur in susceptible individuals with low levels of antibodies only when a second, different factor induces an increase in antibody level sufficient to produce blisters (Ahmed et al., 1993Ahmed A.R. Mohimen A. Yunis E.J. et al.Linkage of pemphigus vulgaris antibody to the major histocompatibility complex in healthy relatives of patients.J Exp Med. 1993; 177: 419-424Crossref PubMed Scopus (77) Google Scholar). This factor(s) can be either genetic or environmental as drugs, burns, viruses, ultraviolet radiation and other heterogeneous triggers (Chorzelski et al., 1971Chorzelski T.P. Jablonska S. Beutner E.H. Kowalska M. Can pemphigus be provoked by burn?.Br J Dermatol. 1971; 85: 320-325Crossref PubMed Scopus (50) Google Scholar;Beutner and Chorzelski, 1976Beutner E.H. Chorzelski T.P. Studies on ethiological factors in pemphigus.J Cutan Pathol. 1976; 3: 67-74Crossref PubMed Scopus (45) Google Scholar;Ruocco et al., 1980Ruocco V. Vitale O. Astarita C. Transient pemphigus induced by sunburn.J Cutan Pathol. 1980; 7: 429-430Crossref PubMed Scopus (17) Google Scholar; Ruocco et al., 1996Ruocco V. Wolf R. Ruocco E. Baroni A. Viruses in pemphigus: a casual or causal relationship?.Int J Dermatol. 1996; 35: 782-784Crossref PubMed Scopus (42) Google Scholar;Ahmed and Rosen, 1989Ahmed A.R. Rosen G.B. Viruses in pemphigus.Int J Dermatol. 1989; 28: 209-217Crossref PubMed Scopus (27) Google Scholar;Brenner et al., 1993Brenner S. Wolf R. Ruocco V. Drug-induced pemphigus. I. A survey.Clin Dermatol. 1993; 11: 501-505Abstract Full Text PDF PubMed Scopus (71) Google Scholar;Cremniter et al., 1998Cremniter D. Baudin M. Roujeau J.C. Prost C. Stressful life events as potential triggers of pemphigus.Arch Dermatol. 1998; 134: 1486-1487Crossref PubMed Scopus (33) Google Scholar;Tur and Brenner, 1998Tur E. Brenner S. Diet and pemphigus. In pursuit of exogenous factors in pemphigus and fogo selvagem.Arch Dermatol. 1998; 134: 1406-1410Crossref PubMed Google Scholar), proved to be important in facilitating the outbreak of pemphigus. In conclusion, although the etiology of pemphigus still remains unknown, it appears that, like in other autoimmune diseases, genetic predisposition is a condition necessary but not sufficient for the onset of the disease which will develop only when one or more additional factors intervene. Dedicated to the memory of Dr. Ciro Manzo. The authors thank Dr. Ernesto de Angelis (Experimental Oncology D-Pharmaco-Chemiotherapy, National Cancer Institute, Napes, Italy) for his critical review of the manuscript. This work has been partially supported by a grant from the Ministero della Sanità, Ricerca Finalizzata ‘90 and by a grant from the Consiglio Nazionale delle Ricerche (CNR, 97-04262-CT04)." @default.
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• W2002135246 cites W2003661326 @default.
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• W2002135246 cites W2013603872 @default.
• W2002135246 cites W2014421311 @default.
• W2002135246 cites W2015284085 @default.
• W2002135246 cites W2018155538 @default.
• W2002135246 cites W2019799755 @default.
• W2002135246 cites W2026442867 @default.
• W2002135246 cites W2029675210 @default.
• W2002135246 cites W2031216870 @default.
• W2002135246 cites W2035407782 @default.
• W2002135246 cites W2039540763 @default.
• W2002135246 cites W2047309488 @default.
• W2002135246 cites W2050179219 @default.
• W2002135246 cites W2052803026 @default.
• W2002135246 cites W2056884449 @default.
• W2002135246 cites W2058143679 @default.
• W2002135246 cites W2070384392 @default.
• W2002135246 cites W2073281335 @default.
• W2002135246 cites W2080986404 @default.
• W2002135246 cites W2089835279 @default.
• W2002135246 cites W2091799436 @default.
• W2002135246 cites W2092016955 @default.
• W2002135246 cites W2094800200 @default.
• W2002135246 cites W2098132847 @default.
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• W2002135246 cites W2100946462 @default.
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• W2002135246 cites W2148542751 @default.
• W2002135246 cites W2159870760 @default.
• W2002135246 cites W2163521262 @default.
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