Do specific pockets of HLA-C molecules predispose Jewish patients to psoriasis vulgaris?

BACKGROUND: Psoriasis vulgaris was reported to be associated with a specific alanine residue at position 73 of HLA-C alleles in Japanese patients. OBJECTIVE: Our purpose was to determine the role of HLA genes in susceptibility to psoriasis vulgaris in the Israeli Jewish population. METHODS: Twenty-eight Israeli patients were analyzed for their HLA class I and II specificities by means of serologic and molecular methods. RESULTS: All patients possessed in their HLA-C antigens an alanine residue at position 73 (p < 0.002). A significantly increased frequency of HLA-Cw6 and of Cw7 was also observed among the patients (p < 0.02). CONCLUSION: Our study clearly shows that alanine in position 73 is significantly associated with psoriasis vulgaris in Jewish patients. Cw6 and Cw7 have a unique antigen-binding pocket containing both alanine at position 73 and a negatively charged aspartic acid at position 9. These residues are most probably important in determining the conformation of the C pocket and in turn the nature of the peptide bound to it. We suggest that this combination confers the highest risk of the development of psoriasis vulgaris.

Effect of zinc therapy on neutrophil chemotaxis in psoriasis.

Neutrophil chemotaxis in patients with psoriasis vulgaris and psoriatic arthritis was investigated before and after 6 weeks of treatment with zinc sulphate (50 mg elementary zinc three times daily). In patients with active psoriasis vulgaris, a significant increase in neutrophil random migration and directed chemotaxis was demonstrated (10.2 +/- 3.1 and 14.1 +/- 4.1 mu, respectively, greater than that of control patients), while in patients with psoriatic arthritis the values were within the normal range (5.8 +/- 3.2 and 1.1 +/- 4.1 mu, respectively, greater than that of control patients). Although the zinc sulphate treatment had little or no effect on the course of either disease, it restored both the random migration and directed chemotaxis to normal values in psoriasis vulgaris patients. These results support the contention that zinc sulphate modifies neutrophil inflammatory potential; however, the lack of a clinical benefit suggests that neutrophils play only a secondary role in the pathogenesis of psoriasis.

A newly characterized HLA DQ beta allele associated with pemphigus vulgaris.

The inheritance of particular alleles of major histocompatibility complex class II genes increases the risk for various human autoimmune diseases; however, only a small percentage of individuals having an allele associated with susceptibility develop disease. The identification of allelic variants more precisely correlated with disease susceptibility would greatly facilitate clinical screening and diagnosis. Oligonucleotide-primed gene amplification in vitro was used to determine the nucleotide sequence of a class II variant found almost exclusively in patients with the autoimmune skin disease pemphigus vulgaris. In addition to clinical implications, the disease-restricted distribution of this variant should provide insight into the molecular mechanisms underlying associations between diseases and HLA-class II genes.

Detection of disease-specific restriction fragment length polymorphisms in pemphigus vulgaris linked to the DQw1 and DQw3 alleles of the HLA-D region.

Pemphigus vulgaris in Israeli Ashkenazi and non-Ashkenazi Jews and in Austrian non-Jewish patients is strongly associated with the DR4 and DRw6 alleles of the HLA-D region class II genes. Restriction fragment length polymorphism analysis was undertaken with DQ beta, DQ alpha, and DR beta cDNA probes. Hybridization with the DQ beta probe identifies Pvu II, BamHI, and EcoRV fragments that absolutely discriminate pemphigus vulgaris patients from healthy DR-, DQ-, and ethnic-matched controls. In contrast the DQ alpha and DR beta probes failed to identify disease-specific restriction fragment length polymorphism fragments. These studies indicate that DQw1 and DQw3 polymorphisms carried by pemphigus vulgaris patients may be directly involved in predisposition to the disease or may be tightly linked to the susceptibility gene itself. To our knowledge, this is the first example of an HLA restriction fragment length polymorphism that is highly associated with susceptibility to autoimmune disease.

Erythroderma and pneumonitis induced by penicillin?

Penicillin and its derivatives are known to cause several dermatologic and pulmonary hypersensitivity reactions. This report describes a patient who presented with combined generalized exfoliative dermatitis and severe pneumonitis caused by penicillin and aggravated by ampicillin, methicillin and mezlocillin. Antibiotic challenges with penicillin caused immediate reappearance of the dermatological manifestation; reactivation of the pneumonitis was probably prevented by immediate discontinuation of the drug.