Biomedical subjects
K K Mittal
Publications and source records attributed to K K Mittal.
Lung puncture aspiration in the diagnosis of acute pneumonias.
The present study was carried out in 100 children of acute pneumonia to establish the diagnosis of etiologic agents. Clinico-radiological assessment and routine investigations including sputum, throat swab and blood culture did not help in identifying the offending micro-organisms. The bacteriological examination of lung puncture aspirate was the most satisfactory tool for the etiological diagnosis. Direct smear examination/culture were positive in 50% aspirates. On cytology, definite epithelioid granulomas indicated tuberculous infection. However, in direct smear/culture negative patients, predominant mononuclear cell infiltration in the aspirated material may indicate non-pyogenic infection. Staphylococcus aureus (22%) was the commonest organism causing pneumonia in the present study.
HLA associations and ancestry in Vogt-Koyanagi-Harada disease and sympathetic ophthalmia.
A strong association with HLA antigens DR4, DRw53, and Bw54 has previously been reported among Japanese patients with Vogt-Koyanagi-Harada disease (VKH) and sympathetic ophthalmia (SO). In the United States, no firm association between HLA-A or -B loci and VKH has been found previously; testing for HLA-DR loci has not been performed to date. The authors performed HLA typing of 23 American patients with VKH and 8 patients with SO. When VKH patients were compared with racially matched controls without disease and patients with other types of uveitis, strong associations with HLA-DR4 and HLA-DRw53 were found. The strongest associations observed in this sample were with HLA-DQw3, an antigen which is in positive linkage disequilibrium with DR4, and with the HLA-DR4/DQw3 haplotype. The small number of patients with SO precluded statistical analysis; however, similar HLA associations were noted. The patients also were questioned regarding their ancestry. The anecdotal association of VKH with American Indian ancestry was confirmed. It appears that the ethnoracial association may be explained by HLA type. One possible explanation for identical HLA associations in two diseases with different precipitating events yet similar ocular manifestations is development of an altered immune response to exogenous microbial antigen with subsequent autoimmunity. Further definition of the genetic susceptibility to VKH and SO may help define the pathophysiology of both diseases and allow the prediction of which patients are at increased risk for SO.
Lymphocyte proliferative responses of patients with ocular toxoplasmosis to parasite and retinal antigens.
In vitro lymphocyte proliferative responses to purified toxoplasma antigens and the retinal S-antigen were evaluated in 40 patients with ocular toxoplasmosis; 16 (40%) had a positive in vitro response to the retinal S-antigen. The proliferative responses to the 2G11 (p22) toxoplasma membrane antigen approached that of a crude antigen preparation of Toxoplasma gondii, whereas the response to the 1E11 immunodominant p30 membrane antigen was considerably less striking. HLA typing was also performed, and none correlated to S-antigen or toxoplasma reactivity. The evidence strongly suggests that patients with a clearly infectious ocular disorder may have part of their disease mediated by a putative autoimmune mechanism. An immune response to the 2G11 toxoplasma antigen may increase the risk of developing ocular disease or a substrain of toxoplasma with 2G11 as its immunodominant membrane antigen may have a greater affinity for the retina.
Clinical and immunopathological studies of pars planitis in a family.
We examined a family in which two brothers with identical HLA typing have pars planitis with snowbanking. Immunopathological studies of one of their eyes showed that in the area of snowbanking over the pars plana there was mild to moderate inflammatory cell infiltration, consisting of mostly Pan T (Leu 4+) lymphocytes. The ratio of T helper/inducer to T suppressor/cytotoxic cells was approximately 10:1. Few macrophages (OKM1+) were identified. Very few B cells and no NK cells were observed. Some retinal vessels had a perivascular infiltration consisting of mostly T lymphocytes. Most of the inflammatory cells bore class II antigens (HLA-DR+), while T cells bore few IL-2 receptors (anti-TAC+). The snowbank consisted mainly of glial elements (GFAP+) and basement membrane components (type IV collagen and laminin) with the predominant cell the Müller cell (Mü+). A site of inflammation at the iris-ciliary body junction also stained for B cells (Leu 14+). These findings suggest that the snowbank could be formed by the glial elements of the peripheral retina. The chronic inflammation in pars planitis appears to consist of helper T cells, both in the pars plana, and the retinal vasculature.
A cell line and clones of lymphocytes from a healthy donor, with specificity to S-antigen.
Retinal-specific antigens can induce autoimmune diseases in eyes of immunized experimental animals and are thought to be involved in certain uveitic conditions in man. We have recently found that peripheral blood lymphocytes from a large proportion of healthy donors react in culture against the retinal S-antigen (S-Ag), when tested by a modified sensitive assay. The investigation of this responsiveness was extended by isolation and characterization of a cell line and clones specific to S-Ag from the blood of a healthy donor. Characterization of the cell line and clones by flow cytometry showed that these lymphocytes carried antigens specific for helper/inducer T cells (CD3 and CD4). The response of the cell line and clones to S-Ag depended completely on added antigen-presenting cells (APC), and was MHC-restricted; no response was observed in cultures with APC carrying incompatible MHC antigens. The cell line and clones reacted to S-Ag considerably more vigorously than the freshly collected blood lymphocytes from the same donor. These data thus provide additional support to the notion that lymphocytes with reactivity toward retinal specific antigens are present in the circulation of normal donors. The possibility that such cells could be involved in pathogenic autoimmune processes in the eye is discussed.
Allelic segregation of HLA-Bw73 from B7.
We report here the reaction pattern of a local serum (C2487) with antigens B7 and Bw73, and data from an intercross family in which B7 and Bw73 antigens segregate as alleles.
A murine monoclonal antibody specific for a novel broad antigen associated with HLA-Bw4.
Serological analysis of the reactivity of a murine monoclonal antibody, HA113, towards lymphocytes from a random panel of 85 cell donors, and members of four families, indicated that HA113 recognizes a public specificity, which is different from the classical Bw4 antigen as defined by human alloantisera.
An anti-I-A murine monoclonal antibody which cross-reacts with HLA-DR2.
A murine monoclonal antibody, 12.7G3, directed against an Ia antigen encoded by genes in the I-Ab subregion of the H-2 genetic complex, was found to be cytotoxic against human B lymphocytes. When tested against a random panel of normal human donors, the reactivity of 12.7G3 exhibited a correlation coefficient of 0.58-0.68 with cells expressing HLA-DR2. Antibody reactivity segregated with HLA-DR2 in two families studied. Binding of 12.7G3, as detected by immunofluorescence using flow microfluorometry, was positive for two human cell lines, GM 3161 and HFB-1, both expressing HLA-DR2, and negative for two other cell lines, GM 3104 (DR1,1) and GM 3164 (DR4,4).
A significant increase of HLA-DR3 and DR2 in systemic lupus erythematosus among blacks.
We found a highly significant increase in the incidence of HLA-DR3 and DR2 antigens in black patients with systemic lupus erythematosus (SLE). HLA-DR3 was found in 62% of patients and 20% of controls (p less than 0.0001), and DR2 in 41% of patients and 18% of controls (p less than 0.001). The relative risk (RR), conferred by DR3 was 6.41, and that by DR2 was 3.03. Further, 84% of the patients had DR3 and/or DR2; the combined RR for SLE with these antigens was 9.0. A significant proportion of the patients (57%) developed lymphocytotoxic antibodies; of these, 19% had HLA specific antibodies.
Overincubation as a moderator in binding HLA antigens with corresponding antibodies as regards HLA-C locus typing.
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Immunobiology of the human major histocompatibility complex: association of HLA antigens with disease.
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Association of HLA-Bw35 with tuberculosis in the Chinese.
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Enhancement of reactivity of HLA-Cw antisera by extending the incubation time.
HLA-Cw antisera showing weak cytotoxic activity when tested at 1 1/2 hours in the conventional HLA-A,B, Cw testing procedure, were found to react better in the test using an extended incubation period of 3 hours. Of the 71 sera which were tested, 15 (21%) sera demonstrated an increase in anti-HLA-Cw reactivity against cells from donors possessing the corresponding Cw antigen. In addition, the use of B cells in the testing procedure appeared to be more favorable than T cells in the enhancement of reactivity of weak HLA-Cw antisera.
Cross reactivity in the HLA region.
Cross-reactivity in the HLA region was studied by adsorbing each of 33 monospecific HLA antisera individually with known platelets from 90 different donors. The residual cytotoxicity following adsorption in each combination of platelet sample and antiserum was assessed against known homologous target lymphocytes. This study has confirmed a majority of the previously known cross-reactive pattern and has revealed new patterns. A more significant observation is that allelic cross-reactivity of broad antigens such as A9, A10 and Bw16, was somewhat narrowed to a given split of these antigens in several instances; e.g., cross-adsorption of A1 antiserum by Aw24, and not Aw23; of A2 antiserum by A26, and not A25; and of B5 antiserum by Bw39, and not Bw38.
Human histocompatibility antigens (HLA).
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Cytotoxicity of a non-HLA serum towards lymphocytes from blood group B, Lewis negative and ABH secretor individuals.
Seven serum samples from a multiparous Hispanic woman (Cano) were found to be lymphocytotoxic against 2% of the cell donors in a large multiethnic cell panel. The reactivity of these sera segregated independently of the HLA region. The lymphocytotoxicity of Cano sera appeared associated with the simultaneous presence of red cell antigen B, Le (a-b-), and ABH secretor status. It could be adsorbed out by red cells from Cano-reactors, but not by those from Cano-non-reactors. Cano sera are clearly detecting a non-HLA antigen on lymphocytes. The exact relationship between this new immunogenetic system (Cano) and the ABO, Lewis and Secretor systems remains to be elucidated.
Birdshot retinochoroidopathy associated with HLA-A29 antigen and immune responsiveness to retinal S-antigen.
Antigen HLA-A29 was present in 16 of 20 patients (80%) with birdshot retinochoroidopathy, but only in 31 of 418 controls (7.4%) (P less than .0001). The relative risk for this disease in persons possessing HLA-A29 antigen was 49.9, one of the highest reported. Of the 20 patients, 13 were also tested for evidence of an in vitro mitotic immune response to purified retinal S-antigen. Of these, 12 (92.3%) responded to the purified preparation, whereas one responded only to a crude retinal homogenate. The histopathologic and clinical findings in an eye from one of the responders to the S-antigen were similar to those in the disease induced in monkeys with the S-antigen. Our findings suggested that birdshot retinochoroidopathy has a genetic predisposition and that retinal autoimmunity, resulting from the S-antigen or other retinal antigens, plays a role in the manifestation of this disease.