Susan H. Hsu

Association of the HL-A7 Cross-Reacting Group with a Specific Reaginic Antibody Response in Allergic Man

A relatively small proportion (17 percent) of individuals highly allergic to ragweed were found to develop marked reaginic (immunoglobulin E-mediated) skin sensitivity to a minor ragweed pollen allergen Ra5 (molecular weight 5200). Sensitivity to Ra5 was significantly associated with the possession of a major histocompatibility antigen of the HL-A7 cross-reacting group. This appears to be the first evidence of a strong association between a specific immune response and a specific group of closely related HL-A antigens in man.

Genetics of human immune response to allergens

In today’s economically developed societies, IgEmediated allergic responses are regarded more as a hindrance than a help. Nevertheless, the ability to make such responses has probably played an important role in protecting our distant ancestors from the scourges of parasitic disease and, indeed, this function is probably still important in many underdeveloped countries.’ We may, therefore, regard the current relatively high prevalence of atopic allergy in the Western world as an unwanted vestige of a previously useful immune function. It seems likely that a genetic capacity toward hyperresponsiveness of the IgE system and concomitant high prevalence of allergy have exerted a weak selective disadvantage in white Europeans since Neolithic times, as parasitic disease became a decreasingly less severe problem. In modem man, the main selective pressure on specijc immune response has almost certainly been infectious disease-in particular, that caused by pathogens which strike before puberty with a high rate of mortality. Several authorP5 have argued convincingly that many of today’s common infectious diseases probably evolved only in the last 5,000 or 6,000

Combined immunodeficiency and vaccine related poliomyelitis in a child with cartilage hair hypoplasia

Patients previously described with cartilage-hair hypoplasia, a distinctive form of short-limbed dwarfism, have been found to have deficient cell-mediated immunity with intact antibody-mediated immunity. The patient with cartilage-hair hypoplasia described in the present report is unusual in that she had both deficient antibody-mediated immunity and deficient cell-mediated immunity. In addition, she developed severe, vaccine-related paralytic poliomyelitis. This complication suggests that live viral vaccines should not be administered to children with short-limbed dwarfism until the form of short-limbed dwarfism is established and immunologic evaluation is performed when indicated.

Intra-HLA recombinations localizing the 21-hydroxylase deficiency gene within the HLA complex

Close linkage between HLA and the gene for 21-OH deficiency causing congenital virilizing adrenal hyperplasia (CVAH) has been well documented. HLA-A/B and HLA/GLO recombination data placed the CVAH gene within the HLA-A to GLO interval, with CVAH invariably segregating with HLA. HLA-A,B,C,DR and GLO typing and ACTH stimulation to determine carrier status was done on seven families. Carrier status correlated with the appropriate HLA haplotypes in all offspring, with two exceptions. Two intra-HLA recombinants were detected in one three-generation family. The father of the proband is homozygous for HLA-A2,Cw2,B27 but is a DR2/DR4 heterozygote. The CVAH gene segregated with DR2 in all but one of his offspring who is a carrier and is DR4. This finding is consistent with recombination between the CVAH gene and DR. Study of the fathers family confirmed synteny of the CVAH gene and DR2. Three of four sibs of the father inherited this haplotype and were CVAH carrier, as was the paternal grandmother, whose other haplotype was A1, Bw44,DR1. One of the fathers sibs was shown serologically to be a HLA-B/D maternal recombinant and a noncarrier. she inherited the A1,Bw44 of one maternal haplotype, but the DR2 of the other. In both recombinants in this family the CVAH gene segregated with the A to B interval, separate from D. While we cannot determine whether the CVAH gene is in the HLA-A to B or B to D interval, this is the first report of two intra-HLA recombinations in one family that unequivocally map the CVAH gene inside HLA-D.

Management of male hyperprolactinemic hypogonadism.

A 30-year-old man with a prolactin secreting pituitary adenoma and hypogonadism was studied. Except for hyperprolactinemia, the results of his pituitary function tests were perfectly normal. Although the mechanism is uncertain, hyperprolactinemia alone may interfere with male reproductive function. The patients impotence and infertility were successful managed with injections of human menopausal gonadotropins (HMG). Adverse interaction between gonadotropins and prolactin along the hypothalamic-pituitary-testis axis may be corrected by HMG injections in certain cases.

Occurrence of paternal and maternal HLA-B/D recombinants in a single family.

Two B/D recombinant offspring in one family were identified by HLA-A,B,C,D, and DR typing with the Eighth International Workshop sera and cells, intrafamily MLC and PLT test. Restimulation of cells primed against the four parental haplotypes showed good discrimination between family members who shared the D alleles and those who did not. When the B/D recombinant haplotypes were primed, accelerated proliferative response was observed only with cells sharing the HLA-D region. Cells that shared with the priming cells the HLA-A to B interval but differed for the D region did not restimulate. These results demonstrated the role of HLA-D disparity in evoking secondary proliferative response and showed that the determinant(s) mapping between HLA-A and B did not restimulate.

Human T Cell-M Φ Collaboration Across Allogeneic Barrier

We have documented the existence of HLA-linked Ir genes to (H,G)-A-L, (T,G)-A-L [1], (Phe,G)- A-L, GAT [2] and GLO MΦ (antigen-presenting cells, APC) are required for specific lymphoproliferative responses to these antigens, as illustrated in Table 1. We have observed that GAT and (T,G)-A-L induced lymphoproliferation was achieved by the addition of either nonirradiated or irradiated autologous MΦ, or by coculturing with 24-h antigen-pulsed autologous MΦ Antigen-pulsed MΦ elicited lymphoproliferation comparable to that of unseparated PBLs cultured continuously with free antigen. Heat-killed MΦ (63 °C for 1 h) were incapable of restoring the proliferative response.