British Journal of Dermatology (1976) 95, 173.
HL-A antigens and vitiligo* G.RETORNAZ, H.BETUEL,t J.P.ORTONNE, AND J.THIVOLET Department of Dermatology, Pavilion R, Hopital E. Herriot, 69374 Lyon, Cedex 2, and t Tissue-typing laboratory of the Blood-Grouping Department, 01 Beynost, France. Accepted for publication 2 December 1975
SUMMARY
HL-A antigens were found with similar frequency in ninety vitiligo patients and in 341 healthy controls. However there was a significant correlation between HL-A 13 and vitiligo with antithyroid antibodies. This supports the concept that vitiligo is a syndrome rather than a disease.
Up to now, no specific or constant biological marker is characteristic of vitiligo. As striking relationships have been found between HL-A antigens and various diseases, the present study was undertaken to look for an association between vitiligo and the presence or absence of these antigens and to detect any possible correlation between them and aetiological, clinical or biological features.
MATERIAL AND METHODS
Ninety unrelated vitiligo patients (56 women and 34 men) of caucasoid origin were studied between October 1974 and April 1975. Diagnosis was based on clinical signs. • For HL-A typing, a two-stage technique of microlymphocytotoxicity was used according to Mittal (1968) with slight modifications (Betuel et al., 1975). Ten antigens of the first locus were screened for: HL-A I, 2, 3, 9, 10, II, W 28, W 29, W 30, W 32, and fifteen antigens of the second locus: HL-A 5, 7, 8, 12, 13, 14, 17, 27, W5, 10, 15, 16, 18, 21, 22. At least two different antisera were used to define each antigen. The control panel consisted of 341 healthy blood donors from Lyon whose HL-A phenotypes had been clearly defined. To estimate the degree of association between an HL-A antigen frequency in the patients and in the control group, the relative incidence ratio of Woolf was used. The relative risk hp(i-hc) X= _ is calculated from the antigen frequencies as found in patients (p) and in controls (c). Chi-square (x^) was calculated according to Woolf's method, the P value was multiplied by the number of HL-A antigens tested. A difference at the 5% level was considered as significant {P corrected). * Parts of this paper are constituents of the thesis of Mrs Retornaz-Picchiottino: 'Les Groupes HL-A en Dermatologie. Revue bibliographique. Etude personnelle dans 90 vitiligos et 14 sclerodermies'. Lyon 1975 no. 305. 173
174
G.Retomaz et al. RESULTS
The comparison between the ninety vitiligo patients and 341 controls does not show any significant difference in HL-A antigen frequency. The same findings apply to the different subsets arranged according to sex, extent of skin lesions, involvement of the pigmentary system of hair follicles, and provocation by an external cause. Interesting results were obtained when age at onset was considered. When the group of patients, in whom the onset of vitiligo was before 25 years, was compared to the controls, a high incidence of HL-A 12 was apparent. The high chi-square gives a corrected P value just short of significant. So, no HL-A type is a valid diagnostic and prognostic clue. Twenty-three related cases of vitiligo (sisters, parents or grandparents) did not differ in their antigen frequency from cases with no family history of the disease. In a three-generation family, four of the five members afflicted with vitiligo were HL-A typed. No haplotype appeared to be correlated with the skin disease. Four of the ninety patients had thyroid disease, and sixteen patients had one relative with thyroid
TABLE I. HL-A antigens in vitiligo patients with and without antithyroid antibodies
HL-A antigen
Antithyroid antibodies + (n == 13)
Antithyroid antibodies — (n == 44)
No.
No.
%
Relative risk
/o
HL-A I
2
15-4
7
2
9
28
3 9
I
69-2 77
2
15-4
l8-2
10
1
9-1
0-83
II
I
I
23
W28 29 30
I
5
II-4
2
77 77 77 77 154 77 77
8 4
1-28 0-19 0-81 358 0-64 1-75 0-96
I
13
2
45
7
15-9
I
9 8 4
2-3 20-8 18-2 91
34-1
32
I
HL-A 5
I
7 8
0 2
154
12
6 4 3
46-1 30-8
15
0
15-9 63-6 29-5
23-1
3
0
0
2
I
77
3
231
3 6
10
I
77
2
15
0
0
2
2-27 6-8 45 6-8 136 45 45
16
0
0
I
23
3 4 4
6-8
13 14 17 27
W 5
18
2
154
21
0
0
22
2
154
I
91 9-1
0-96
3-58 0-32 0-15 1-81
1-65 19-1
4-09 0-62 113
1-89 1-75 0-62 1-07
2-48 0-33 1-81
HL-A antigens and vitiligo
175
disorder. In this group of twenty patients the HL-A distribution pattern was similar to that of the other vitiligo patients and the healthy controls. Thirteen vitiligo patients with antithyroid antibodies (detected by a double layer immunofiuorescence technique) (Guinet et al, 1967) were compared to forty-four patients without these antibodies and to the 341 controls (Table i). An increased frequency of HL-A 13 was apparent: four patients (30-8%) had this antigen as compared to fourteen controls (4-i%). The relative risk is 10-3; the high chi-square 12-57 gives a P value
HL-A antigens and vitiligo* G.RETORNAZ, H.BETUEL,t J.P.ORTONNE, AND J.THIVOLET Department of Dermatology, Pavilion R, Hopital E. Herriot, 69374 Lyon, Cedex 2, and t Tissue-typing laboratory of the Blood-Grouping Department, 01 Beynost, France. Accepted for publication 2 December 1975
SUMMARY
HL-A antigens were found with similar frequency in ninety vitiligo patients and in 341 healthy controls. However there was a significant correlation between HL-A 13 and vitiligo with antithyroid antibodies. This supports the concept that vitiligo is a syndrome rather than a disease.
Up to now, no specific or constant biological marker is characteristic of vitiligo. As striking relationships have been found between HL-A antigens and various diseases, the present study was undertaken to look for an association between vitiligo and the presence or absence of these antigens and to detect any possible correlation between them and aetiological, clinical or biological features.
MATERIAL AND METHODS
Ninety unrelated vitiligo patients (56 women and 34 men) of caucasoid origin were studied between October 1974 and April 1975. Diagnosis was based on clinical signs. • For HL-A typing, a two-stage technique of microlymphocytotoxicity was used according to Mittal (1968) with slight modifications (Betuel et al., 1975). Ten antigens of the first locus were screened for: HL-A I, 2, 3, 9, 10, II, W 28, W 29, W 30, W 32, and fifteen antigens of the second locus: HL-A 5, 7, 8, 12, 13, 14, 17, 27, W5, 10, 15, 16, 18, 21, 22. At least two different antisera were used to define each antigen. The control panel consisted of 341 healthy blood donors from Lyon whose HL-A phenotypes had been clearly defined. To estimate the degree of association between an HL-A antigen frequency in the patients and in the control group, the relative incidence ratio of Woolf was used. The relative risk hp(i-hc) X= _ is calculated from the antigen frequencies as found in patients (p) and in controls (c). Chi-square (x^) was calculated according to Woolf's method, the P value was multiplied by the number of HL-A antigens tested. A difference at the 5% level was considered as significant {P corrected). * Parts of this paper are constituents of the thesis of Mrs Retornaz-Picchiottino: 'Les Groupes HL-A en Dermatologie. Revue bibliographique. Etude personnelle dans 90 vitiligos et 14 sclerodermies'. Lyon 1975 no. 305. 173
174
G.Retomaz et al. RESULTS
The comparison between the ninety vitiligo patients and 341 controls does not show any significant difference in HL-A antigen frequency. The same findings apply to the different subsets arranged according to sex, extent of skin lesions, involvement of the pigmentary system of hair follicles, and provocation by an external cause. Interesting results were obtained when age at onset was considered. When the group of patients, in whom the onset of vitiligo was before 25 years, was compared to the controls, a high incidence of HL-A 12 was apparent. The high chi-square gives a corrected P value just short of significant. So, no HL-A type is a valid diagnostic and prognostic clue. Twenty-three related cases of vitiligo (sisters, parents or grandparents) did not differ in their antigen frequency from cases with no family history of the disease. In a three-generation family, four of the five members afflicted with vitiligo were HL-A typed. No haplotype appeared to be correlated with the skin disease. Four of the ninety patients had thyroid disease, and sixteen patients had one relative with thyroid
TABLE I. HL-A antigens in vitiligo patients with and without antithyroid antibodies
HL-A antigen
Antithyroid antibodies + (n == 13)
Antithyroid antibodies — (n == 44)
No.
No.
%
Relative risk
/o
HL-A I
2
15-4
7
2
9
28
3 9
I
69-2 77
2
15-4
l8-2
10
1
9-1
0-83
II
I
I
23
W28 29 30
I
5
II-4
2
77 77 77 77 154 77 77
8 4
1-28 0-19 0-81 358 0-64 1-75 0-96
I
13
2
45
7
15-9
I
9 8 4
2-3 20-8 18-2 91
34-1
32
I
HL-A 5
I
7 8
0 2
154
12
6 4 3
46-1 30-8
15
0
15-9 63-6 29-5
23-1
3
0
0
2
I
77
3
231
3 6
10
I
77
2
15
0
0
2
2-27 6-8 45 6-8 136 45 45
16
0
0
I
23
3 4 4
6-8
13 14 17 27
W 5
18
2
154
21
0
0
22
2
154
I
91 9-1
0-96
3-58 0-32 0-15 1-81
1-65 19-1
4-09 0-62 113
1-89 1-75 0-62 1-07
2-48 0-33 1-81
HL-A antigens and vitiligo
175
disorder. In this group of twenty patients the HL-A distribution pattern was similar to that of the other vitiligo patients and the healthy controls. Thirteen vitiligo patients with antithyroid antibodies (detected by a double layer immunofiuorescence technique) (Guinet et al, 1967) were compared to forty-four patients without these antibodies and to the 341 controls (Table i). An increased frequency of HL-A 13 was apparent: four patients (30-8%) had this antigen as compared to fourteen controls (4-i%). The relative risk is 10-3; the high chi-square 12-57 gives a P value
