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Human type V (tartrate-resistant) acid phosphatase belongs to a unique group of iron-binding proteins that includes uteroferrin and other purple phosphatases. The enzyme is normally restricted to osteoclasts and certain phagocytic cells but its rôle is unknown. We show that phosphatase mRNA is abundant in cells of monohistiocytic phenotype and that enzyme expression in cultured human monocyte-derived macrophages is depressed by gamma-interferon and bacterial lipopolysaccharide, agents that promote functional differentiation in these cells. In contrast, phorbol ester, which stimulates intracellular calcium-mediated events, greatly enhances type V phosphatase expression and mRNA abundance. Lymphokine and phorbol ester-modulated expression of type V acid phosphatase expression thus represents a model system for investigating proliferative responses that are specific to cells of the mononuclear macrophage system.

The unknown allele that predisposes to the development of haemochromatosis in man has been localized to the HLA class I region on the short arm of chromosome 6. We have utilized pulsed-field gel electrophoresis in conjunction with probes that map within, or in the vicinity of, this region to search for structural lesions that may further define the disease locus. Using the enzyme Mlu I, fragments that associated specifically with the HLA-A23, A31 and B8 alleles were identified. However, in members of three pedigrees affected by haemochromatosis, and in six unrelated patients with the disorder, no disease-specific differences were detected in the DNA fragments with four restriction enzymes and eight probes when compared with healthy individuals. These data suggest that the lesion responsible for hereditary haemochromatosis lies beyond the resolution of this technique and does not involve large structural deletions or extensive re-arrangements in this highly polymorphic region of the genome.

The class III complement proteins (C2, BF, C4A, and C4B) were studied in 57 multicase rheumatoid arthritis (RA) families. When the gene frequencies for RA probands were compared to a normal control panel (162 haplotypes), a significantly higher frequency of the rare variant C4B*3 was observed (p less than 0.05). No significant differences were seen for the other C2, BF, C4A, or C4B alleles. The most common haplotype found in the probands was HLA-Cw5,B44,C2*C,BF*S,C4A*3,C4B*3,DR4, occurring with a frequency of 0.088. Haplotypes containing HLA-DR4 and Bw62 were found to carry either C4A*3,C4B*3; C4A*3,C4B*1; or C4A*4,C4B*2. When only haplotypes containing DR4 were compared between probands and controls, the frequency of the C4B*3-bearing haplotype remained higher in the probands. It is concluded that Bw62,C4A*3,C4B*3DR4 is a haplotype which is especially associated with RA. The low frequency in the RA population of this haplotype indicates that C4B*3 has a minor role in overall RA susceptibility.

Susceptibility to systemic lupus erythematosus (SLE) is known to be governed by genes in the HLA region of the 6th chromosome. From previous studies it has not been possible to distinguish between the effects of null genes for the complement component C4 and HLA-DR3, because of the marked linkage disequilibrium between DR3 and a null allele of C4A (C4A QO) in caucasoid populations. We report here an immunogenetic study of 44 cases of SLE, selected because they were DR3 negative. Eighteen of the 30 Caucasoid cases (60%) had extended HLA haplotypes with a C4 null allele, compared with 22 of 60 (37%) of a control panel of 60 DR3 negative normal Caucasoid subjects. This difference is significant (chi 2 = 4.41; 0.05 greater than P greater than 0.01). Of 14 non-caucasoid patients analysed, 10 had a C4 null allele. It is concluded that the null alleles of the C4 A and B genes are themselves directly responsible for conferring susceptibility to SLE.