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The prevalence of HLA-B12 and HLA-B7 antigens in primary open-angle glaucoma.

HLA-B12 antigen was found in 50% and HLA-B7 was present in 49% of patients with primary open-angle glaucoma. Either one of the antigens B12 or B7 was noted in 88% of such glaucoma patients. The prevalences of B12, B7, or of either antigen were much greater in patients with primary open-angle glaucoma than in the general population or in patients with normal intraocular pressure. The prevalences in patients with ocular hypertension (IOP greater than 20 mm Hg) were intermediate between the ocular normotensives and the patients with primary open-angle glaucoma. The close association between HLA-B12 and HLA-B7 and primary open-angle glaucoma suggested immunologic components of the disease and possible convenient genetic markers.

Glaucoma

The association of HLA antigens A3, B7, and DW2 with 330 multiple sclerosis patients in the United States.

Reported associations of HLA antigens with MS have varied considerably. In this study we have examined 330 clinically definite MS patients from the United States. The frequency of DW2 (52%) was highly statistically significant in MS patients as compared to controls (p less than 0.00001). Neither A3 nor B7 was significantly increased in MS; however, the joint occurrences of A3-DW2 (20% vs 7%, p less than 0.001) and B7-DW2 (30% vs 13%, p less than 0.0002) are highly associated with MS.

Chromosome Mapping

HLA antigens in allergic contact dermatitis.

The relationship between HLA factors and allergic contact dermatitis was examined in a series of 149 patients with unequivocal positive reactions to one or several allergens on epicutaneous testing. Nine statistically significant associations involving 6 different HLA antigens and 6 different allergens were found. Four allergens (chromium, formalin, balsam of Peru and wool alcohol) were positively associated with the B7 antigen. Furthermore chromium allergy was associated with A3, formalin allergy with A2 (negative association) and A9, nickel allergy with B8 and colophony allergy with B27. The B7 antigen and the combination A3+B7 showed significant regressions on number of allergies. The results fit the hypothesis that some HLA factors (like B7) may predispose for multiple contact allergy and others for allergen specific reactions.

Adult

Purification of immunologically active HLA-A and -B antigens by a series of monoclonal antibody columns.

Serologically and biochemically pure preparations of detergent and papain-solubilized HLA-A2 and HLA-B7 antigens were isolated by high pH elution from a series of immunoaffinity columns constructed from monoclonal antibodies with specificity for HLA-A2 and HLA-B7 antigens. These preparations retained the immunological activity and quaternary structure of the native molecule and should provide suitable reagents for insertion into liposomes and probing the role of major histocompatibility antigens in lymphocyte interactions.

Animals

A double-blind trial of transfer factor vs placebo in multiple sclerosis patients.

A double-blind trial of the effect of transfer factor on multiple sclerosis patients was carried out. In a series of fifty-six multiple sclerosis patients treated with monthly injections of either transfer factor or placebo for 1 year, no beneficial effect of transfer factor was noted. In addition, none of the immunological and serological parameters studied (measles migration inhibition, measles HI titre or CSF immunoglobulin) changed as a result of transfer factor therapy. Histocompatibility typing and CSF IgG/TP ratios were correlated with the disease activity. Of interest was the finding that the presence of the DW2 antigen, when unassociated with HLA-B7 antigen, appeared to correlate with the mildest form of disease activity.

Adult

HLA antigens and affective disorders.

A total of 168 patients with different types of affective disorders were examined with respect to their HLA antigens. The frequency of the A10 antigen was found to be increased in the patients particularly in those with the unipolar type of disease. The frequency of the A1 antigen was decreased among unipolar patients. A decreased frequency of the B7 antigen was found in the total material of patients, and in particular in those with a bipolar type of disease. Our results were in disagreement with findings by other investigators. So far there is no conclusive evidence for association between any HLA antigen and affective disorders.

Affective Symptoms

Familial Hodgkin's disease and the major histocompatibility complex.

Two sisters who developed nodular sclerosis Hodgkin's disease (H.D., N.S.) within 3 months of their 25th birthdays were HLA and MLC identical. All family members possessed the HLA-B7 antigen. The propositi, a third HLA/MLC identical sister, and the mother, shared the maternal B7 and lacked Dw2. The father and a fourth sibling with the paternal B7 were heterozygous for Dw2. In six unrelated patients with H.D., N.S., the presence of B7 and Dw2 correlated precisely. In 69 consecutive patients with H.D., N.S., the frequencies of 23 HLA antigens did not differ significantly from the frequencies in 245 control subjects.

Adult

Genetics of cell-mediated lympholysis in man.

Cell-mediated lympholysis (CML) was studied in a family containing two siblings in who genetic recombinaiton had occurred in the HLA comples. In one sibling, recombination occurred between the HLA-A locus and the HLA-B locus. In the second sibling recombination occurred between the HLA-B locus and the HLA-D locus. Strong CML activity was generated in mixed lymphocyte cultures (MLC) when stimulator and responder cells differed in HLA-A, B, and D antigens. MLC involving HLA-D differences alone did not generate CML. Weak, but definite CML activity was generated during MLC with cells differing at HLA-A and HLA-B but sharing HLA-D. HLA-B antigens were good targets for lysis in all combinations studied. HLA-A antigens were poor targets in some but not in all combinations. However, combinations where HLA-A antigens seemed to be good targets could have involved HLA-B differences due to polymorphism of HLA-B7 antigens each inherited from a different parent. HLA-D antigens did not serve as targets for lysis. In three cell experiments, excellent CML activity was generated when responder cells were stimulated by HLA-D antigens and by HLA-A and B antigens present on separate stimulator cells.

Adult

HLA antigens and antibody responses to measles and rubella viruses in multiple sclerosis.

Twenty-four HLA-antigens coded by loci A and B were determined serologically for 60 multiple sclerosis patients from Northern Finland. Forty-five of the patients were also typed by mixed leucocyte culture reactivity for HLA-Dw2. The only statistically significant difference in antigen frequencies in these patients compared with those in controls was the decrease of HLA-A2 among patients. Measles and rubella antibody titres in patients with and without HLA-Dw2 and HLA-B7 antigens were compared using a sensitive radioimmunoassay method. There was no difference between age- and sex-matched patient groups.

Adult

Electrophysiological and immunological studies in optic neuritis.

Serial clinical and electrophysiological examinations and immunological investigations have been performed on 34 patients with primary optic neuritis. In 8 patients, the latency of visual evoked responses was normal after the resolution of clinical symptoms, and in a further 5 patients improvement in VER latency occurred although the response remained abnormal. In 17 patients, VER's abnormal and did not alter over the period of clinical recovery; in 4 patients there was a progressive increase in the latency of the VER's through both eyes although a satisfactory clinical recovery occurred. The frequency of histocompatibility antigens was similar in the group of ON patients to that in the normal population. Immunological function was normal in patients with ON as assessed by levels of immunoglobulins. T and B lymphocyte numbers and by lymphocyte blastogenesis in response to PHA and myelin basic protein. Three patients have developed multiple sclerosis, all of whom had either HLA-A3 or -B7 antigens; the clinical and electrophysiological pattern of recovery was different in each case.

Cerebrospinal Fluid Proteins

HLA antigens and primary open-angle glaucoma in black Americans.

Black patients with primary open-angle glaucoma, when compared to nonglaucomatous individuals, demonstrate significantly increased prevalences of the HLA antigens B7 and B12 and significantly decreased frequencies of A1 and A11. White patients with primary open-angle glaucoma have in common with blacks the increases in B7 and B12 and the decrease in A11, but present no deficit of A1. In addition, white patients with primary open-angle glaucoma demonstrate a significant increase of A3 and a decrease of Bw35, both of which are not found in blacks.

Black People

Genetic basis of multiple sclerosis: HLA antigens, disease progression, and oligoclonal IgG in CSF.

The HLA antigens B7 and Dw2 occurred at elevated frequencies in 105 multiple sclerosis (MS) patients (49 and 47%, respectively), compared to healthy controls (29 and 30%), especially in MS patients with oligoclonal CSF-IgG (51 and 50%), in cases with CSF-IgG index values above 1.5 (64 and 64%), and in those with the most malignant course of the disease (47 and 59%). Normal or only slightly elevated frequencies of B7 and Dw2 were found in MS patients without oligoclonal CSF IgG (35 and 29%), normal CSF-IgG index (43 and 39%), and the most benign course (42 and 37%). No correlation was found between the HLA type and measles virus antibody titers in serum or a measles virus antibody response within the CNS.

Adult

The association of histocompatibility antigens of the B7 cross-reacting group with Peyronie's disease.

A significant relationship between Peyronie's disease and histocompatibility antigens of the B7 cross-reacting group is described. The association of Peyronie's disease with a group of immunologically cross-reacting antigens, rather than with a single antigen, suggests that a yet undetermined agent of specific molecular configuration involves in some way its pathogenesis. This finding has diagnostic application and adds a new dimension to the etiologic investigation of Peyronie's disease.

Cross Reactions

Studies on the frequency and associations of islet-cell antibodies in juvenile diabetes mellitus.

Ninety-six juvenile onset type diabetics showed an increase in the frequency of HLA B8 and B15 and a decrease in frequency of HLA B7 antigens. Sixty-four maturity onset diabetics showed no disturbance in the frequency of these antigens. Fifty-four of the juvenile onset type diabetics, with an average duration of disease of 3.2 years were tested for the presence of islet cell antibodies (ICAs). Thirty-two percent were positive, the frequency decreasing from 70% in those patients tested within one year of diagnosis to 0.5% in those patients tested more than 5 years after diagnosis. No correlation was found between HLA type and the frequency of ICAs, but there was an increase in other autoantibodies in B15 positive patients. Preliminary absorption studies suggest a cross reactivity of ICAs and Coxsackie B4 virus.

Adolescent

The pigment dispersion syndrome.

The pigment dispersion syndrome was noted in 10% of white and black subjects with and without glaucoma. This suggested pigment dispersion was not a high risk factor in the development of glaucoma. The HLA-B7 antigen was less prevalent and HLA-B13 and Bw17 antigens were significantly more prevalent in individuals with the pigment dispersion syndrome than in subjects without the syndrome. Either HLA-B13 or Bw17 antigen was found in 23 (77%) of 30 patients with the pigment dispersion syndrome and in only 13 (6%) of the 203 subjects without pigment dispersion. Pigmentary glaucoma was characterized by a significantly higher prevalence of combinations of HLA-B12 and B13 or HLA-B12 and Bw17 antigens as compared to the pigment dispersion syndrome without glaucoma, primary open-angle glaucoma, or the general population. This suggested that pigmentary glaucoma differed genetically from primary open-angle glaucoma and was a separate entity.

Glaucoma

A functional enzymatic assay as potential readout for a clinical trial of a schistosomiasis vaccine.

An estimated 200 million people are currently infected with schistosomiasis and an additional 800 million reside in high transmission-risk areas in 78 endemic countries. In this report we describe a functional enzymatic assay based on the core calpain antigen (Sm-p80) of the schistosomiasis vaccine, SchistoShield®. A 44 kDa soluble variant of the core Sm-p80 antigen (B7), was assessed for its enzymatic activity using a fluorescent synthetic substrate. Inhibition of the B7 enzymatic activity by Sm-p80-specific antibodies obtained from pre-clinical trials in rodents, non-human primates as well as from participants of the human clinical trials was measured. The B7 enzyme activity followed a Michaelis-Menten-like kinetic behavior. Statistically significant inhibition of the B7 activity was observed by Sm-p80-specific antibodies produced by immunized mice, non-human primates and humans. This quantitative serological assay could be of value in assessing the effectiveness of the SchistoShield® vaccine in human trials in Africa.

Journal Article

Immunological features of juvenile onset diabetic patients correlated to HLA type.

Ninety-six juvenile onset type diabetics showed an increase in the frequency of HLA B8 and B15 and a decrease in frequency of HLA B7 antigens. Sixty-four maturity onset diabetics showed no disturbance in the frequency of these antigens. Fifty-four of the juvenile onset type diabetics, with an average duration of disease of 3.2 years were tested for the presence of islet cell antibodies (ICAs). Thirty-two per cent were positive, the incidence decreasing from 70% in those patients tested within 1 year of diagnosis to zero in those patients tested within 1 year of diagnosis to zero in those patients tested more than 5 years after diagnosis. No correlation was found between the incidence of ICAs and either cell-mediated immune reactions or HLA type. B15 positive patients were associated with cell-mediated immune reactions to pancreatic antigens and with the presence of other tissue autoantibodies. HLA phenotypes were not associated with environmental data. Diabetic siblings had identical HLA A-B haplotypes more often than could be expected to occur by chance.

Adolescent