Is serum the optimal source for HLA antibodies?

The cytotoxic reactivity of 18 predefined class I HLA serum antibodies was compared with that of antibody preparations containing anticoagulants. ACD-A, EDTA, 4% citrate and heparin plasmas all showed lower cytotoxicity than serum antibodies. Recalcification of both platelet-rich and platelet-poor ACD-A plasma did not fully restore the antibody reactivity, suggesting a detrimental effect of calcium chelation. This effect was exclusive of volume or of any platelet or plasma protein involvement. The changes in pH contributed to the lower reactivity and to the increased lympholytic effect, whereas adjusting the pH toward the serum value improved the reactivity. Heat-inactivated antibodies showed only a slightly reduced cytotoxicity. Heparin had the least effect of all anticoagulants on the reactivity, although in heparin there was a definite dose-dependent decline in cytotoxic titer which was probably related to anticomplementary activity. Calcium chelators, such as EDTA and citrate, showed marked cytotoxic inhibition at half the usual complement concentration. This effect was more pronounced when the anticoagulant and lymphocytes were incubated prior to cytotoxicity testing. At the complement concentrations used, the inhibitory effects of the citrate anticoagulants appeared to be primarily calcium-related. Inhibition tests, serial titrations and testing of varying calcium concentrations confirmed the superiority of serum as antibody source.

HLA antigens in psoriatic arthritis.

HLA antigen frequencies were studied in 158 patients with psoriatic arthritis, and compared to those of 101 patients with uncomplicated psoriasis and 243 healthy controls. The HLA antigens B16, B17, B27, B39 and Cw6 were associated with psoriatic arthritis. No associations between DR antigens and psoriatic arthritis were demonstrated. However, the subset of patients with rheumatoid-like arthritis demonstrated an increase in DR4. Uncomplicated psoriasis patients had higher frequencies of B17, Cw6 and DR7 than patients with psoriatic arthritis, while B7 and B27 correlated with development of arthritis. HLA-B27, Cw2 and DRw52 were associated with back involvement, whereas B38 and B39 were associated with polyarthritis. HLA-B7, B13 and DR7 correlated with milder disease in patients with psoriatic arthritis.

Discordance between HLA-B27 and ankylosing spondylitis: a family investigation.

Forty-one members in 4 generations of a family were evaluated clinically for ankylosing spondylitis (AS). Thirty-five individuals were HLA typed. The propositus and 4 male siblings demonstrated AS. A sister had sacroiliitis. Three of the affected sibs shared the B27 containing haplotype, but the remaining 3 individuals lacked the B27 but shared the other maternal haplotype. Two other first degree relatives with B27 did not show evidence of either sacroiliitis or AS. Four members of the family had psoriasis, but did not all share a common haplotype. The lack of association of known HLA antigens with disease expression in this family suggests a role for a putative disease susceptibility gene for psoriasis in the development of B27 negative spondylitis and illustrates the difficulty with the diagnosis of B27 negative AS, since when the family was first studied, it presented as a family of "pure" AS and only after several years of followup did the first evidence of psoriasis appear.

An investigation of nonhemolytic transfusion reactions.

This study was undertaken to document the incidence of immediate, nonhemolytic transfusion reactions and to identify a technique or set of techniques that would best identify the different causes of these reactions. A variety of tests were employed to detect lymphocyte, granulocyte, platelet and anti-IgA antibodies. During this study 26,318 units of blood components were transfused on 5,030 occasions. 191 immediate, nonhemolytic reactions were experienced giving an incidence per unit of 0.73%. Blood specimens from 101 of these patients were investigated along with serum from 57 patients who showed no reaction to transfusion as controls. We show that standard B cell lymphocytotoxicity testing is the technique with which most antibodies can be detected (64% of reactors positive vs. 30% of controls, p less than 0.001). Additional tests did not significantly increase the level of antibody detection.

Splits of the HLA DR2 antigen.

The reaction of ninety DR2 positive persons with 20 anti-DR2 sera were studied. Four of the panel and members of two families did not react with two of these anti-DR sera and were considered to have the short-split "DR2.2". DR2 positive samples reacting strongly with all anti-DR2 were designated "DR2.1".

HL-A frequencies in patients with multiple sclerosis.

The histocompatibility antigens (HL-A) have been determined in 100 multiple sclerosis (M.S.) patients and 140 randomly selected controls. In the M.S. group there was a statistically significant increase in the frequency of HL-A 7 and W 18 with an insignificant increase in HL-A 3. The variance from normal HL-A patterns in the M.S. population may play some role in establishing the substrate for this disease. Studies in experimental animals have shown that susceptibility to autoimmune disease and to virus infection is linked to the major histocompatibility locus. This has interesting implications for both the "slow virus" and the "autoimmune" theories of the etiology of multiple sclerosis.