Molecular Heterogeneity of the Fourth Component of Complement (C4) and its Genes in Vitiligo

• Published in: Journal of investigative dermatology Vol. 99; no. 6; pp. 853 - 858
• Main Authors: Venneker, Gerard T, Westerhof, Wiete, de Vries, Ivan J, Drayer, Nick M, Wolthers, Bert G, de Waal, Leo P, Bos, Jan D, Asghar, Syed S
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01-12-1992; Nature Publishing
• Subjects: Adrenal Hyperplasia, Congenital - genetics; Adrenal Hyperplasia, Congenital - immunology; Alleles; Biological and medical sciences; Complement C2 - genetics; Complement C2 - physiology; Complement C4 - chemistry; Complement C4 - genetics; Dermatology; Family Health; Female; Gene Deletion; Histocompatibility Testing; HLA Antigens - analysis; Homozygote; Humans; Male; Medical sciences; Pedigree; Pigmentary diseases of the skin; Proteins - physiology; Steroid 21-Hydroxylase - genetics; Vitiligo - genetics; Vitiligo - immunology; Human; Immunopathology; HLA-System; Skin disease; Allele; Vitiligo; Complement C2; Major histocompatibility system; Class II histocompatibility antigen; Complement C4; Inheritance; Immune deficiency
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12614826

In view of evidence suggesting vitiligo is an autoimmune disease, we investigated whether vitiligo is associated with inherited deficiencies of the fourth (C4) and second (C2) component of complement and with certain human leukocyte antigens (HLA). Analysis of functional activities of C4 and C2 in sera of patients with vitiligo (n = 42) showed that 17% of them had a heterozygous C4 deficiency and 5% had a heterozygous C2 deficiency. In the normal control group (n = 30), 3% had a heterozygous C4 deficiency and none had a C2 deficiency. C4 typing by Western blot analysis showed the frequency of the C4A*Q0 allele in the vitiligo patient group to be close to normal. However, the frequency of one C4B*Q0 allele was three times higher, and that of two C4B*Q0 alleles five times higher in the vitiligo patient group than the reported frequencies in normal control groups. Southern blot analysis of Taq1 digests of DNA using C4 and 21-hydroxylase probes showed that two patients with two C4B*Q0 alleles had a deletion of a 21-OHA-C4B segment. In the other patients, having one or two C4B*Q0 alleles, these null alleles probably occurred due to a loss of C4 gene expression. HLA analysis did not show any allelic association of C4A*Q0 or C4B*Q0 with any HLA antigen in vitiligo, but confirmed the previous findings of a negative association with HLA-DR3 and a positive association with HLA-DR4. These results suggest that abnormalities of the C4B gene and the above-mentioned associations with HLA antigens may be some of the risk factors in vitiligo.