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

Venneker, G.T.; Westerhof, W.; Vries, I J de; Drayer, N.M.; Wolthers, B.G.; Waal, L. P. de; Bos, Jan D.; Asghar, Syed S.

doi:10.1111/1523-1747.ep12614826

Cited by 34 publications

(29 citation statements)

References 31 publications

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“…These include LMP-1 and -7 (low-molecular-mass polypeptide-2 and -7) and TAP-1 and -2 (transporter associated with antigen processing protein-1 and -2) [144]. Homozygous or heterozygous complement 2 and 4 deficiency is associated with autoimmunity, and this has been described in vitiligo [145]. The CTLA-4 gene product down-regulates T-cell activation and controls T-cell apoptosis.…”

Section: Vitiligo and Autoimmunitymentioning

confidence: 99%

Vitiligo, reactive oxygen species and T-cells

2010

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The acquired depigmenting disorder of vitiligo affects an estimated 1% of the world population and constitutes one of the commonest dermatoses. Although essentially asymptomatic, the psychosocial impact of vitiligo can be severe. The cause of vitiligo remains enigmatic, hampering efforts at successful therapy. The underlying pathogenesis of the pigment loss has, however, been clarified to some extent in recent years, offering the prospect of effective treatment, accurate prognosis and rational preventative strategies. Vitiligo occurs when functioning melanocytes disappear from the epidermis. A single dominant pathway is unlikely to account for all cases of melanocyte loss in vitiligo; rather, it is the result of complex interactions of biochemical, environmental and immunological events, in a permissive genetic milieu. ROS (reactive oxygen species) and H2O2 in excess can damage biological processes, and this situation has been documented in active vitiligo skin. Tyrosinase activity is impaired by excess H2O2 through oxidation of methionine residues in this key melanogenic enzyme. Mechanisms for repairing this oxidant damage are also damaged by H2O2, compounding the effect. Numerous proteins and peptides, in addition to tyrosinase, are similarly affected. It is possible that oxidant stress is the principal cause of vitiligo. However, there is also ample evidence of immunological phenomena in vitiligo, particularly in established chronic and progressive disease. Both innate and adaptive arms of the immune system are involved, with a dominant role for T-cells. Sensitized CD8+ T-cells are targeted to melanocyte differentiation antigens and destroy melanocytes either as the primary event in vitiligo or as a secondary promotive consequence. There is speculation on the interplay, if any, between ROS and the immune system in the pathogenesis of vitiligo. The present review focuses on the scientific evidence linking alterations in ROS and/or T-cells to vitiligo.

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Section: Vitiligo and Autoimmunitymentioning

confidence: 99%

Vitiligo, reactive oxygen species and T-cells

2010

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“…The total classical and alternative pathway, C4, C2 and factor B activities were measured by hemolytic assays already described in detail [18]. The normal range for the classical and alternative pathways was 68-130%, for C4 68-126%, for C2 72-132% and for factor B 70-130% of the normal serum pool.…”

Section: Complement Assaysmentioning

confidence: 99%

“…Analysis of genomic DNA by Southern blotting was carried out essentially as described previously [18]. Genomic DNA (5 Ìg) of each individual was digested to completion with the restriction enzyme Taq1 (Boehringer, Mannheim, Germany) according to the manufacturer's instructions and electrophoresed in 0.6% agarose gels.…”

Section: Analysis Of Genomic Dnamentioning

confidence: 99%

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Molecular Heterogeneity of Second and Fourth Components of Complement and Their Genes in Systemic Sclerosis and Association of HLA Alleles A1, B8 and DR3 with Limited and DR5 with Diffuse Systemic Sclerosis

Venneker¹,

Hoogen²,

Meegen³

et al. 1998

Exp Clin Immunogenet

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Deficiency of the complement component C4 at the functional, protein and gene level and deficiency of complement component C2 at the functional level were investigated and HLA analysis was performed on patients with limited and diffuse systemic sclerosis (SSc). One of the patients with limited SSc (n = 15) had subnormal C4, 1 subnormal C2 and 1 subnormal C4 and C2 activities; the latter patient had HLA alleles A11;B35;Dw1 associated with type II C2 deficiency and therefore most likely had a defect at the C2 locus. One of the patients with diffuse SSC (n = 12) had subnormal C4 and 1 subnormal C4 and C2 activities. C2 deficiencies in patients other than the one with the haplotype associated with C2 deficiency appeared not to be determined by the gene at the C2 locus. The incidence of partial C2 deficiency in a normal Caucasian population is reported to be 16 in 10,000, and that of partial C4 deficiency also appears to be very low. The percentages of C4A*Q0 and C4B*Q0 alleles in normal controls (n = 45) were within the reported range. Seven patients with limited SSc (n = 14) had one or two C4A*Q0 alleles and 2 with diffuse SSc (n = 13) had one C4A*Q0 allele. Thus, the incidence of C4A*Q0 was higher than normal in limited SSc and within the normal range in diffuse SSc. The two-sided Fisher’s exact test applied on these data revealed that the association of C4A*Q0 with limited SSc did not reach a significant level (p = 0.10). Two of the 3 patients with limited SSc, who had two C4A*Q0 alleles, carried a heterozygous C4A-21-hydroxylase A (OHA) gene segment deletion as detected by Southern blotting. There was no correlation between the subnormal activity of C4 and the occurrence of one or two C4A*Q0 (and C4A-21-OHA segment deletion). HLA alleles A1, B8 and DR3 (p = 0.002) were associated with limited SSc (n = 23) and DR5(w11) (p = 0.018) with diffuse SSc (n = 17).

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“…15,16 There are reports in literature about positive association of vitiligo with HLA-DR4 antigen and negative association with HLA-DR3 antigen. 17 Because of HLA gene polymorphism, the results of these reports may vary according to the population studied. 18 A high incidence of HLA-DRw12 and -A2 antigens was detected in a population of Caucasian Germans.…”

Section: Vitiligomentioning

confidence: 99%

Antígenos de histocompatibilidade humanos e dermatologia: da pesquisa para a prática clínica

Alves

Vieira

Meyer

et al. 2006

An. Bras. Dermatol.

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Abstract:The participation of the human histocompatibility system (HLA: human leukocyte antigens) in the pathogenesis of autoimmune diseases is well known. Situated on the short arm of chromosome 6, the HLA system is very polymorphic and has the capacity to confer susceptibility or resistance to different diseases. In Dermatology, this system has an important participation in the pathogenesis and natural course of various diseases. The strength and type of association differ with conditions and sometimes with the ethnic-racial group studied. The discovery of molecular methods to typify HLA alleles and recent updates in its nomenclature has contributed to a better understanding of this system. Unfortunately, this information has not been adequately transmitted in the literature, hindering identification of the association of the HLA with skin diseases. In this review, some aspects of the HLA system are discussed, such as methods of detection, nomenclature and association with vitiligo, pemphigus, psoriasis, lupus erythematosus, scabies, cutaneous leishmaniasis, leprosy, paracoccidiodomycosis and atopic dermatitis.

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

Cited by 34 publications

References 31 publications

Vitiligo, reactive oxygen species and T-cells

Vitiligo, reactive oxygen species and T-cells

Molecular Heterogeneity of Second and Fourth Components of Complement and Their Genes in Systemic Sclerosis and Association of HLA Alleles A1, B8 and DR3 with Limited and DR5 with Diffuse Systemic Sclerosis

Antígenos de histocompatibilidade humanos e dermatologia: da pesquisa para a prática clínica

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