HLA antigens and vitiligo in an American black population.
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Biomedical subjects
Publications and source records attributed to K K Mittal.
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Divergent observations suggest that genetic factors contribute to the susceptibility to or clinical course of idiopathic pulmonary fibrosis. To determine whether there is an association between the major histocompatibility (HLA) system and idiopathic pulmonary fibrosis, the distribution of 35 antigens of HLA loci A and B was determined among 33 white patients with idiopathic pulmonary fibrosis and 329 healthy white control subjects. Although certain antigens tended to be more prevalent among patients with idiopathic pulmonary fibrosis compared with control subjects, there were no significant differences in the phenotype frequencies of the HLA-A and HLA-B antigens between these 2 groups. Thus, although subtle associations may exist between the HLA loci and idiopathic pulmonary fibrosis, these results indicate that antigens of the HLA-A and HLA-B loci are not linked with major risk factors in this disease.
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The immunogenic properties of HLA-A9 antigens isolated from serum have been evaluated. A9 antigens at various stages of purification can elicit the formation of cytotoxic antibodies which become operationally specific to A9 either after absorption of the xenoantisera with cultured human lymphoid cells or human red blood cells, or after dilution of xenoantisera with human serum. A9 xenoantisera do no affect mixed lymphocyte reactions between allogeneic lymphocytes carrying A9, suggesting that coating of antigens of the A locus does not impair the functional activity of lymphocytes in the mixed lymphocyte reaction.
Four out of 8 thrombocytopenic patients without detectable cytotoxic antibodies to human peripheral lymphocytes contained cytotoxic antibodies to cultured human lymphoid cells. The presence of such antibodies was associated with reduced survival of infused allogeneic platelets in these patients. The antibodies reacted in a distinct fashion with a panel of cultured human lymphoid cells and are directed to B cell antigens. Cytotoxic antibodies to cultured human lymphoid cells did not react in vitro with platelets suggesting that the antibodies play no significant role in the accelerated destruction of infused allogeneic platelets, although their presence predicts it. Therefore, screening of sera with cultured human lymphoid cells appears to be a useful test in addition to those now used to select patients for transfusion of allogeneic platelets. Sera from polytransfused patients without cytotoxic antibodies to peripheral lymphocytes may be a useful source of antibodies to B cell antigens.
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Antisera were raised in rabbits against leukaemic lymphosarcoma (LSL) cells which carried surface markers of both thymus-derived T lymphocytes (T cells) and bone marrow-derived B lymphocytes (B cells). After absorption with leucocytes, erythrocytes and serum proteins from normal individuals, the antisera demonstrated significant complement-dependent cytotoxicity against leukaemic cells from patients with acute lymphoblastic leukaemia (ALL) (9/11), LSL (7/9) and chronic lymphocytic leukaemia (CLL) (9/12), with an antibody titre of 1:64 or greater. The antisera did not react with: (a) blood lymphocytes from clinically healthy individuals (0/23), patients with ono-lymphoproliferative disorders (0/8) and normal umbilical cords (0/3), (b) normal lymphocytes stimulated by pokeweed mitogen (0/7), allogeneic lymphocytes (0/3), fetuin (0/1), purified protein derivative (PPD) (0/2), and candida antigen (0/1); (C) normal marrow cells (0/3), (D) normal thymocytes (0/2) and (E) leukaemic cells from patients with acute myeloblastic (AML) (0/10) and chronic granulocytic leukaemia (CGL) (0/3). However, the antisera did react with lymphoblastoid cells from continuous B-cell lines derived from an AML patient and from a non-leukaemic individual and, to a lesser extent, with lymphocytes from patients with infectious mononucleosis. The antisera also reacted with lymphocytes from chronically infected tonsils. Cytotoxicity of the antisera against lymphoblastoid and tonsillar cells was inhibited by ALL and CLL cell-lysates; and, conversely, cytotoxicity against ALL cells was inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal inhibited by the lymphoblastoid cell extract. In contrast, a cell lysate or extract from normal lymphocytes did not inhibit cytotoxicity toward lymphoblastoid, tonsillar or ALL cells. Cytotoxicity of the antisera was neutralized by a goat anti-rabbit IgG (GAR IgG). These results suggest that the antisera contained antibodies reactive with antigens possibly common to neoplastic lymphocytes, tonsillar cells, lymphoblastoid cells and some lymphocytes from patients with infectious mononucleosis.
Lymphocytotoxic or thrombocytolytic antibodies were detected in 11 of 25 thrombocytopenic patients receiving repeated platelet transfusions. Platelet survival times were reduced in these patients (half-life [T/2], 32 hours) as compared to patients without antibody (T/2, 51 hours, P less than .05). In one woman with acute myeloblastic leukemia and a potent platelet antibody, combination chemotherapy resulted in a profound decrease in circulating gamma-globulin and concurrent disappearance of the cytotoxic antibody. The survival of transfused platelets in this patient was dramatically improved, and bleeding was controlled.
In order to study a possible hereditary factor leading to multiple sclerosis (MS) susceptibility, histocompatibility (HL-A) types were studied in families where two or more first-degree relatives had MS. Neither the inheritance of a particular parental HL-A chromosome, nor the occurrence of any specific HL-A antigens, could be shown to be necessary or sufficient for the development of MS in family members. The distribution of HL-A chromosomes was essentially the same for affected and unaffected family members. An excess of 3,7 haplotype and W21 antigen was demonstrated, both in affected patients and in unaffected family members, in equal proportions. We conclude that the HL-A chromosome has no direct causal relationship to MS susceptibility, although it may be indirectly associated by population stratification, maternal factors, or some other mechanism.
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Murine strains vary greatly in their content of natural antibodies to human lymphocytes; sera from NZB, B10.BR/TSn, DBA/J, and B10.S mice reacted with more than 90% of the panel of human lymphocytes, yet those from other strains did not react. These levels of natural antibodies to human lymphocytes did not correlate with the H-2 type of mice, but appeared to be a dominant character with incomplete penetrance. Since sera from germfree mice also contained natural antibodies to human lymphocytes, their formation was not influenced substantially by bacteria.
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From two families, one with Clr deficiency and the other with C6 deficiency, evidence was obtained suggesting genetic independence between the transmission of a 50% deficit in the functional activity of these two complement components and the inheritance of the HL--A system, the ABO system, and the sex of individuals.
Remarkable differences were observed when 1,465 healthy Caucasian individuals and 128 healthy Negro individuals were compared for the genetic distribution of 25 different HLA antigens. Caucasians had a significantly higher frequency of A1, A3, B8, and Bw16, and Negroes of A28 and Aw30. The haplotype which had the highest incidence as well as the greatest positive linkage disequilibrium was A1-B8 among Caucasians and A2-B12 among Negroes. Genetic distance between the two races was 0.0592. The 89 Caucasian patients with renal failure did not demonstrate any significant deviations in phenotype frequencies (PF) of various antigens, when compared with healthy Caucasians; however, 48 similar Negro patients had twice as high an incidence of Bw17 as the healthy Negroes. No significant deviation in PF was observed in 77 Caucasian patients who had leukemia; however, 32 Caucasian patients who had back pain (24 also had back stiffness) due to spondylitic, arthritic or disc syndrome, had a significant increase of Bw16 and of B27, and a decrease of B12, when compared to Caucasian controls.
Evidence for ankylosing spondylitis was sought by clinical, radiologic, and ophthalmologic examination in HL-A W27-positive men, aged 18 or older, selected from a tissue-donor population. Back pain of 3 months' duration or longer (P less than 0.05), back stiffness, restricted lumbar flexion and chest expansion, sacroiliac erosions (P less than 0.05) and sclerosis, and ophthalmologic sequels of anterior uveitis were found more often in the 24 men of the W27 group than in a control group of 31 men lacking this antigen. Based upon accepted criteria, 3 W27 persons had definite spondylitis and an additional 3 W27 persons and one control subject had findings strongly suggestive of spondylitis (P less than 0.05). This striking frequency, if extrapolated to the general population, would place approximately 1 of 4 W27-positive men at risk for this disease.
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