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Persistent polyclonal B-cell lymphocytosis (PPBL) is an intriguing disorder diagnosed predominantly in women, usually cigarette smokers, characterized by an increase in the number of polyclonal B lymphocytes. Abnormality of the B-cell population is also evidenced by the presence of multiple bcl-2/Ig gene rearrangements and the finding of an additional long arm chromosome 3q+ (i3)(q10) within a significant proportion of B cells. The physiopathology of PPBL is unknown but its association with the HLA DR7 phenotype suggests a possible genetic disorder. To further determine whether PPBL has a genetic predisposition, we have undertaken an extensive study in a large family of a patient diagnosed with PPBL. Three individuals among the first-degree relatives presented all the criteria for a diagnosis of PPBL. A slight increase in serum IgM without evidence of B-cell proliferation was shown in two additional siblings. Multiple bcl-2/Ig gene rearrangements, a typical feature of PPBL, were identified in 8/10 individuals among first-degree relatives. A statistically significant association was found between the presence of these rearrangements and of a paternal HLA haplotype. We conclude that PPBL has a familial occurrence suggesting an underlying genetic defect. The development of the complete syndrome probably relies on unidentified additional co-factors.

Familial Kaposi's sarcoma and familial Paget's disease of bone have not previously been reported to occur in the one patient or the one family. We report on an 82-year-old female of Lebanese descent who was recently diagnosed with Kaposi's sarcoma and Paget's disease. Of the patient's eight siblings, seven had Paget's disease and two of these also had Kaposi's sarcoma. Histocompatibility leucocyte antigen (HLA) class I and II typing of the patient showed: A2, A3; B35, Bx; Bw6; Cw4; DR beta 1*1101 (an HLA-DR5 subtype), DR beta 3 and DQ beta 1*0301. Previous reports have described possible associations of familial Kaposi's sarcoma with HLA-DR5 and Paget's disease with DR2. DR beta 1*1104, DP beta 1*04 and DQw1. Genetic factors and possible viral aetiologies for each condition are reviewed.

Human leukocyte antigens (HLA-A, -B, -C, and -DR loci) and possible associations with occupational allergy to laboratory animals and atopy indicators were studied in laboratory animal workers with airway symptoms (n = 92) and in those who were symptom free (n = 27), as well as in a population reference group of blood donors in good health (n = 123). The laboratory animal workers, but not the population reference group, were allergologically examined with skin prick testing to common environmental and animal allergens together with measurement of total serum IgE levels. Seven HLA antigens, i.e., HLA-A9, -B5, -B12, -B16, -DR4, -DR5, and -Drw6, suggested possible associations with symptoms and/or atopy indicators. When correcting the p-values for the number of studied antigens, only the HLA-B16 differences remained statistically significant. HLA-B16 was elevated in symptom-free subjects compared to the population reference group and in subjects with serum IgE < 10 kU/L. Subjects with serum IgE > 100 kU/L and sensitized against environmental and/or laboratory animals, including LAA asthmatics, lacked HLA-B16. It is suggested that HLA-B16 or an immunosuppressive gene linked to HLA-B16 reduce the risk of producing IgE antibodies against animal protein allergens. However, our a priori hypothesis of a possible risk associated with HLA B15-DR4 could not be confirmed.

The incidence of pregnancy loss is higher in patients with various autoimmune diseases than in the general population. The causes of recurrent spontaneous abortions (RSA) are unknown; however, the presence of antinuclear antibodies and other antibodies in some women with RSA who are otherwise healthy suggests the possibility of underlying autoimmune disease. Because autoimmune diseases are often associated with an increased incidence of certain histocompatibility antigens, we examined the occurrence of specific HLA antigens in patients who had been treated for RSA. We found HLA-DR5 to be significantly overrepresented in the patients with RSA who aborted again after treatment with paternal mononuclear cell immunotherapy, compared with the incidence of this phenotype in a control population. Neither antinuclear antibodies nor antilymphocyte antibodies segregated with DR5. However, DR5+ patients who developed antilymphocyte antibodies after immunotherapy were more likely than all other treated patients to experience subsequent abortion (P less than 0.01). Our findings suggest the possibility of an underlying autoimmune disease in these women.