Immunology Letters, 27 (1991) 5 9 - 6 2 Elsevier IMLET 01516
HLA-DR1 is associated with vitiligo A n n a Poloy 1, L a k o s T i b o r l, J. K r a m e r 2, N g u g e n Anh-Tuan 2, E. Kraszits 3, I. Medgyessy 3, G. F/Jst 2, Valeria Stenszky 3 a n d N. R. Farid 4 IPdndy Kdlman County Hospital, Gyula, Hungary, 2National Institute of Haematology, Budapest, Hungary, 3Blood Transfusion Centre, Debrecen, Hungary, and 4Thyroid Research Laboratory, Health Sciences Centre, St. John's, Newfoundland, Canada (Received 9 July 1990; revision received 19 September 1990; accepted 4 October 1990)
1. Summary
In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.
and III alleles in two groups of patients. In Group I the patients belong to families with more than one vitiligo case and/or other autoimmune diseases. Group II consists of vitiligo patients with negative family history for autoimmune disorders (sporadic vitiligo).
2. Introduction 3. Materials and Methods
The aetiopathogenesis of vitiligo is probably autoimmune in nature [1, 2]. Anti-melanocyte antibodies have been demonstrated [3] in the sera of active vitiligo patients. Furthermore, vitiligo patients' sera containing anti-melanocyte antibodies can lyse cultured human melanoc-ytes by both complement activation and antibody-dependent cellular cytotoxicity [4]. Vitiligo is associated with other autoimmune diseases, especially thyroid autoimmune disorders [5, 6], and often, family history of autoimmune diseases is present [7, 8]. The aggregation of vitiligo in some families and its postulated autoimmune nature instigated studies [9, 10] into the association of vitiligo with H L A antigens. Association with a variety of Class I alleles was reported, albeit in patients of different ethnic backgrounds [11, 12]. The disease was related to HLADR4 in Caucasian and black Americans [13, 14] and to DR7 in a small group of Italian patients [15]. The present study was undertaken to look for an association between vitiligo and MHC Class I, II Key words: Vitiligo; Autoimmune disorder; HLA-DRI Correspondence to." Anna Polay M.D., P~indy K~ilman County
Eighty-eight vitiligo patients (51 women, 37 men) 57 of whom were unrelated, were studied. The diagnosis was based on physical examination. All subjects were Caucasian Hungarians. The patients studied were divided into two groups: group I consisted of 66 patients (38 women, 28 men) from 35 families with multiple cases of vitiligo and/or other autoimmune disorders. Their disease included thyroid diseases, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, coeliac disease, alopecia areata. The 35 probands suffered only from vitiligo. In 14 families the probands had affected sibs, in 12 families the probands had one affected sib whereas in two families 3 siblings suffered vitiligo. In group II there were 22 unrelated vitiligo patients (13 women, 9 men) without family history of either vitiligo or other autoimmune diseases. The subjects were typed for 31 H L A A, B, C and for 6 DR locus antigens [16]. The results were compared to those of 160 controls typed for the same antigens. C4 typing was done according to Awdeh and Alper [17] using the modification of Sim and Cross [18]. Gels were evaluated by densitometry [191. Factor B was typed on cellulose acetate membranes [20].
Hospital, Dept. Dermatology, Semmelweis u. 1, Gyula 5700 Hungary. 0165-2478 / 91 / $ 3.50 © 1991 Elsevier Science Publishers B.V. (Biomedical Division)
59
3.1. Statistical analys&
TABLE 2
For the p o p u l a t i o n study the data were analyzed by chi-square significance test, whereas for the analysis o f family data the Green a n d Woodrow [21] a n d the T h o m s o n a n d B o d m e r [22] m a t h e m a t i c a l models were applied. The relative predispositional effects (RPEs) o f the H L A D R alleles [23] was used to assess whether a decrease in the frequency o f a n o t h e r allele is that expected from the increased frequency o f the first allele with which the disease has a strong association (DR1) or is a true negative association.
4. Results and Discussion Table 1 shows the H L A a n t i g e n whose frequencies deviate in the 57 unrelated vitiligo patients. I n comp a r i s o n to n o r m a l controls we f o u n d H L A - D R 1 was significantly ( p < 0 . 0 0 0 1 ) increased. By contrast, H L A - B 8 was (p < 0 . 0 5 ) less frequent in the patient group. W h e n the p a t i e n t material was divided into two groups, the greatest difference f o u n d was that the frequency o f B27 was increased in g r o u p I (p < 0.001) c o m p a r e d to the c o n t r o l g r o u p (Table 1). Again, in group I H L A - B 8 was n o t e n c o u n t e r e d at all [24]. H L A - D R 3 , however, which is in strong linkage d i s e q u i l i b r i u m with B8 in the n o r m a l H u n g a r i a n p o p u l a t i o n , occurred more often (p < 0.05) in this g r o u p c o m p a r e d to controls. O n the other h a n d , the existence o f this linkage d i s e q u i l i b r i u m was d o c u m e n t e d in other family members, p a r t i c u l a r l y
HLA antigen frequenciesdeviating from control and non-related vitiligo patients. HLA antigens
Alone (N= 55)
Patients with vitiligo with additional autoimmune disease (N= 13)
B27 B8 DR1 DR3
7 (12.7) 0 (0) 24 (43.6) 20 (36.4)
4 (30.7) 2 (15.4) 6 (46.1) 8 (61.5)*
The patients here are the members of the families with multiple cases of vitiligoand/or other autoimmune diseases (see Materials and Methods, group 1). Some of them were related as we would have expected 35 probands from the 35 families. *p
HLA-DR1 is associated with vitiligo A n n a Poloy 1, L a k o s T i b o r l, J. K r a m e r 2, N g u g e n Anh-Tuan 2, E. Kraszits 3, I. Medgyessy 3, G. F/Jst 2, Valeria Stenszky 3 a n d N. R. Farid 4 IPdndy Kdlman County Hospital, Gyula, Hungary, 2National Institute of Haematology, Budapest, Hungary, 3Blood Transfusion Centre, Debrecen, Hungary, and 4Thyroid Research Laboratory, Health Sciences Centre, St. John's, Newfoundland, Canada (Received 9 July 1990; revision received 19 September 1990; accepted 4 October 1990)
1. Summary
In Eastern Hungary, vitiligo is found to be associated with HLA-DR1. When other autoimmune disorders are also present, DR3 is also increased.
and III alleles in two groups of patients. In Group I the patients belong to families with more than one vitiligo case and/or other autoimmune diseases. Group II consists of vitiligo patients with negative family history for autoimmune disorders (sporadic vitiligo).
2. Introduction 3. Materials and Methods
The aetiopathogenesis of vitiligo is probably autoimmune in nature [1, 2]. Anti-melanocyte antibodies have been demonstrated [3] in the sera of active vitiligo patients. Furthermore, vitiligo patients' sera containing anti-melanocyte antibodies can lyse cultured human melanoc-ytes by both complement activation and antibody-dependent cellular cytotoxicity [4]. Vitiligo is associated with other autoimmune diseases, especially thyroid autoimmune disorders [5, 6], and often, family history of autoimmune diseases is present [7, 8]. The aggregation of vitiligo in some families and its postulated autoimmune nature instigated studies [9, 10] into the association of vitiligo with H L A antigens. Association with a variety of Class I alleles was reported, albeit in patients of different ethnic backgrounds [11, 12]. The disease was related to HLADR4 in Caucasian and black Americans [13, 14] and to DR7 in a small group of Italian patients [15]. The present study was undertaken to look for an association between vitiligo and MHC Class I, II Key words: Vitiligo; Autoimmune disorder; HLA-DRI Correspondence to." Anna Polay M.D., P~indy K~ilman County
Eighty-eight vitiligo patients (51 women, 37 men) 57 of whom were unrelated, were studied. The diagnosis was based on physical examination. All subjects were Caucasian Hungarians. The patients studied were divided into two groups: group I consisted of 66 patients (38 women, 28 men) from 35 families with multiple cases of vitiligo and/or other autoimmune disorders. Their disease included thyroid diseases, type I diabetes, rheumatoid arthritis, systemic lupus erythematosus, coeliac disease, alopecia areata. The 35 probands suffered only from vitiligo. In 14 families the probands had affected sibs, in 12 families the probands had one affected sib whereas in two families 3 siblings suffered vitiligo. In group II there were 22 unrelated vitiligo patients (13 women, 9 men) without family history of either vitiligo or other autoimmune diseases. The subjects were typed for 31 H L A A, B, C and for 6 DR locus antigens [16]. The results were compared to those of 160 controls typed for the same antigens. C4 typing was done according to Awdeh and Alper [17] using the modification of Sim and Cross [18]. Gels were evaluated by densitometry [191. Factor B was typed on cellulose acetate membranes [20].
Hospital, Dept. Dermatology, Semmelweis u. 1, Gyula 5700 Hungary. 0165-2478 / 91 / $ 3.50 © 1991 Elsevier Science Publishers B.V. (Biomedical Division)
59
3.1. Statistical analys&
TABLE 2
For the p o p u l a t i o n study the data were analyzed by chi-square significance test, whereas for the analysis o f family data the Green a n d Woodrow [21] a n d the T h o m s o n a n d B o d m e r [22] m a t h e m a t i c a l models were applied. The relative predispositional effects (RPEs) o f the H L A D R alleles [23] was used to assess whether a decrease in the frequency o f a n o t h e r allele is that expected from the increased frequency o f the first allele with which the disease has a strong association (DR1) or is a true negative association.
4. Results and Discussion Table 1 shows the H L A a n t i g e n whose frequencies deviate in the 57 unrelated vitiligo patients. I n comp a r i s o n to n o r m a l controls we f o u n d H L A - D R 1 was significantly ( p < 0 . 0 0 0 1 ) increased. By contrast, H L A - B 8 was (p < 0 . 0 5 ) less frequent in the patient group. W h e n the p a t i e n t material was divided into two groups, the greatest difference f o u n d was that the frequency o f B27 was increased in g r o u p I (p < 0.001) c o m p a r e d to the c o n t r o l g r o u p (Table 1). Again, in group I H L A - B 8 was n o t e n c o u n t e r e d at all [24]. H L A - D R 3 , however, which is in strong linkage d i s e q u i l i b r i u m with B8 in the n o r m a l H u n g a r i a n p o p u l a t i o n , occurred more often (p < 0.05) in this g r o u p c o m p a r e d to controls. O n the other h a n d , the existence o f this linkage d i s e q u i l i b r i u m was d o c u m e n t e d in other family members, p a r t i c u l a r l y
HLA antigen frequenciesdeviating from control and non-related vitiligo patients. HLA antigens
Alone (N= 55)
Patients with vitiligo with additional autoimmune disease (N= 13)
B27 B8 DR1 DR3
7 (12.7) 0 (0) 24 (43.6) 20 (36.4)
4 (30.7) 2 (15.4) 6 (46.1) 8 (61.5)*
The patients here are the members of the families with multiple cases of vitiligoand/or other autoimmune diseases (see Materials and Methods, group 1). Some of them were related as we would have expected 35 probands from the 35 families. *p
