Pemphigus vulgaris in siblings: HLA-DR4 and HLA-DQw3 and susceptibility to pemphigus.

BACKGROUND: The association of pemphigus vulgaris with the HLA serotypes, DR4 and DRw6, and with the DQ-beta chain alleles, DQw1 and DQw3, suggests that there is a genetic predisposition to this disease. However, familial cases of pemphigus vulgaris are exceedingly rare. OBJECTIVE: We studied two siblings with pemphigus vulgaris and three unaffected family members to determine whether an HLA allele was associated with the development of pemphigus vulgaris in this family. METHODS: We utilized restriction fragment length polymorphism methods using the HLA-DR beta 1, HLA-DQ alpha, and HLA-DW beta 1 genes as cDNA probes. RESULTS: We found that the affected siblings share the haplotype HLA-DR4 and the DQw.3.2 allele. CONCLUSION: Our findings of gene sharing among siblings with pemphigus vulgaris lend support to previous studies of unrelated Caucasian patients, which implicated DQw3 allele polymorphisms in conferring susceptibility to pemphigus.

Deposition and removal of cutaneous beta 2-microglobulin.

These studies were designed to track the cutaneous deposition of beta 2-microglobulin (beta 2M) in patients on chronic hemodialysis, patients with chronic renal insufficiency and patients with successful renal transplants. Immunoperoxidase staining of skin biopsies from dialysis patients demonstrated significantly increased amounts of beta 2M compared to controls (p < 0.01). There was a strong positive correlation between the skin beta 2M content and the years of dialysis treatment. Renal transplant recipients had decreased skin content of beta 2M compared to hemodialysis patients. There was no difference in the skin beta 2M content in patients with chronic renal insufficiency not on hemodialysis and controls. No dialysis patient had amyloid in the skin by Congo red stain. We conclude that beta 2M accumulates in the skin of patients on chronic hemodialysis. This beta 2M is not in the form of amyloid. Successful renal transplantation allows for the removal of beta 2M from the skin indicating that beta 2M not in the form of amyloid can be mobilized from tissue sites.

The regulatory role of human helper T-cell clones on antithyroid antibody production by peripheral B-cells.

The helper effects of thyroid antigen-specific T-cell clones (TCC) on antibody production by peripheral B-cells were studied and compared with similar effects of self major histocompatibility complex II (MHC-II)-reactive TCC as well as uncloned CD4+ cells. Ten TCC were derived from thyroid tissue or peripheral blood mononuclear cells (PBMC) in patients with Graves' disease. Uncloned CD4+ cells were also obtained from PBMC in patients with autoimmune thyroid disease. All TCC were CD3+/CD4+. B-Cells from patients with mainly high serum levels of microsomal antibodies (McAb) were cultured alone and with either TCC or uncloned CD4+ cells in the presence or absence of thyroid antigens [microsomal antigen/thyroid peroxidase (McAg/TPO) and thyroglobulin (Tg)] or pokeweed mitogen (PWM). Total immunoglobulin G (IgG) and specific thyroid antibodies were measured by enzyme-linked immunosorbent assay. Self MHC-II-reactive TCC induced B-cell production of total IgG and even McAb independent of antigens or PWM. Specific TCC required thyroid antigens to induce antibodies. The optimal McAg/TPO or Tg concentration was 10 ng/mL for total IgG production and 1 ng/mL McAg/TPO for McAb synthesis. The addition of PWM did not affect McAb production, but enhanced total IgG synthesis by B-cells under the influence of some specific TCC. Uncloned CD4+ cells induced both total IgG and McAb synthesis in the presence of PWM. With thyroid antigens, uncloned CD4+ cells induced total IgG synthesis at levels comparable to those of specific TCC, but induced smaller quantities of McAb in the presence of McAg/TPO. Our antigen-specific TCC could, therefore, stimulate specific B-cells to produce thyroid antibodies in vitro. Self MHC-II-reactive TCC could also induce specific antibodies by B-cells. Both self MHC-II-reactive CD4+ cells and antigen-specific CD4 cells may play an important role in the pathogenesis and/or perpetuation of autoimmune thyroid disease.