A study of the prevalence of hepatitis B surface antigen (HBsAg) in cirrhosis of liver by RPHA.
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Biomedical subjects
Publications and source records attributed to S Mathur.
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Sera and secretions from 100 couples with unexplained infertility were tested for sperm antibodies by cytotoxicity and passive hemagglutination and also for antibodies to human leukocyte antigen (HLA) by cytotoxicity assays. Lymphocytes of the study subjects were typed for 61 HLA-A and B alleles. Thirteen of 30 (43%) men with sperm autoimmunity also had HLA antibodies in their serum and/or seminal plasma samples, in contrast to 2 of 35 (6%) nonautoimmune males (P = 0.0003). Twenty-five of 35 (71%) sperm antibody-positive infertile women had HLA antibodies in their sera and/or secretions, while only 7 of 31 (23%) women without sperm antibodies were positive (P = 0.00007). Antibodies to HLA-A19 (A26, A29, AW30, AW31, AW32, AW33, and AW34) and Bw35 (B5, B15, B17, and B18) complexes were present in 19 of 22 (86%) infertile men and 44 of 48 (92%) infertile women positive for HLA antibodies (P less than 0.01). The presence of antibodies to HLA-A19 and/or Bw35 in the infertile subjects did not correlate with the presence of HLA-A19 and/or Bw35 in the husbands. The presence of antibodies to HLA-A19 and/or Bw35 in the cervical mucus of the infertile women correlated with their presence in the seminal plasma of their husbands. It is suggested that antibodies to sperm antigens cross-reactive with HLA-A19 and/or Bw35 may be relevant to infertility.
To assess whether or not immunologic factors in husbands, wives, or both, influence the motility of sperm in the female reproductive tract, hemagglutination and cytotoxicity sperm antibody (Ab) assays and postcoital tests (PCTs) were performed in 293 infertile couples. More couples without male autoimmunity to sperm (64% of 66; P less than 0.001) had greater than or equal to 10 motile sperm per high power field (adequate PCT), as compared with 26% of 122 couples with untreated male autoimmunity, 19% of 77 couples with corticosteroid-treated male autoimmunity without a pregnancy, and 36% of 28 couples with successfully treated male autoimmunity to sperm. Good correlation was obtained among pregnancy achievement, lack of sperm antibodies, and adequate sperm motility in the PCT (P less than 0.0001). Sperm motility in the PCT correlated positively with sperm motility in the semen and inversely with cytotoxic sperm Ab in the serum and seminal plasma of men and women and hemagglutinating sperm Ab in the cervical mucus samples. Sperm motility in the PCT has a predictive value of 72% for male autoimmunity and 57% for female isoimmunity to sperm in the presence of normal cervical mucus and in the absence of infections.
Sperm and T lymphocytes share antigens, and sera from infertile subjects with sperm immunity have agglutinating antibodies to T lymphocytes. In the present study, cytotoxic antibody titers to sperm (C-Sp) and lymphocytes (C-Ly) were measured in sera, seminal plasma, cervical mucus and vaginal secretions of 52 infertile couples. The samples were divided into C-Sp negative and C-Sp positive groups. C-Ly titers against control T lymphocytes were significantly elevated in C-Sp positive sera of 35 males (P less than 0.005) and 27 females (P less than 0.05) as compared with C-Sp negative sera. C-Ly titers against autologous or partner T lymphocytes were similarly elevated in the sera of both groups. Titers of C-Ly in C-Sp positive secretions (seminal plasma, cervical mucus and vaginal secretions) against autologous and partner, as well as control, T lymphocytes were significantly elevated. In addition, elevated titers of C-Ly to autologous, partner and control B lymphocytes were observed in sera, cervical mucus and vaginal secretions from females with sperm immunity. The infertile males, however, did not have significant B lymphocyte immunity. Immunofluorescence assays revealed a significantly higher incidence of sperm and T lymphocyte antibodies (primarily IgG) in the C-Sp positive than in the C-Sp negative group. Titration of 100 sera from infertile subjects (50 couples) against a panel of lymphocytes of known HLA specificities failed to reveal a pattern of activity against HLA antigens of the A, B and C loci. Absorption of immune sera with sperm or lymphocytes reduced C-Sp and C-Ly titers significantly (P less than 0.001). These results suggest that infertile subjects with sperm immunity produce antibodies to cross-reactive antigens present on sperm and T lymphocytes.
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One hundred three infertile couples and 50 fertile couples were tested for the presence of sperm antibodies by passive hemagglutination and cytotoxicity assays and typed for human leukocyte antigens (HLAs) of the A and B loci. Fifty-four percent of the males and 43% of the females with sperm antibodies were found to have the HLA-B7 antigen, in contrast to 19% of a general population (P less than 0.0001). HLA-BW35 (a Workshop antigen of the B locus) was also present at a significantly increased antigenic frequency (P less than 0.00001) in those females with sperm antibodies. Of the 73 infertile couples with sperm antibodies, 79% shared the B7, B8, and/or BW35 alleles. Two of 12 infertile couples and 10 of 50 fertile couples without sperm antibodies shared these alleles. The significant association of HLA-B7 and BW35 alleles with sperm antibodies in infertile subjects suggests a selective disadvantage of these antigens in human reproduction.
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The absolute numbers of B lymphocytes and of total and "active" T lymphocytes in peripheral venous blood (Mv) from 15 females at the time of normal term deliveries were found to be significantly less (p less than 0.001) than in the fetal umbilical vein (Uv) or artery (Ua) or in the peripheral blood of 75 normal nonpregnant controls (Cv), suggesting that maternal cellular immunity at term is lowered. In 19 umbilical artery samples, titers of lymphocytotoxic antibodies (Cyt), expressed as the mean log of reciprocal titer values, were significantly higher (p less than 0.01 in each case)( than in matched maternal samples, against the following cell types: Maternal T cells (7.1 in Ua vs 1.21 in Mv sera); maternal B cells (3.23 vs 1.58); T cells (4.41 vs 1.38) but not B cells from other females at delivery; autologous T cells (2.9 vs 1.0); autologous B cells (1.88 vs 0.69); T (5.39 vs 0.81) and B (2.80 vs 1.25) cells from the paired Uv; T (3.78 vs 0.62) and B (2.64 vs 0.77) cells from the Uv of other newborn infants; and T (4.19 vs 2.0) but not B cells from controls (Cv). The highest Cyt titers in the umbilical artery samples were against maternal T lymphocytes. Immunofluorescence studies indicated that the Cyt antibodies were primarily IgG. Absorption of 13 other Ua sera with maternal T cells eliminated with Cyt activity against both Mv and Cv T cells; absorption with Cv T cells eliminated the reaction against Cv T while reducing cyt titres to Mv T lymphocytes. We conclude that the fetus produces lymphocytotoxic antibody specifically directed against maternal T lymphocytes, in addition to antibody against T lymphocytes of other adults.
Antibody titres to whole ovary, theca cells, granulosa cells and endometrium were determined by passive haemagglutination and immunofluorescence assays in sera and in cervical and vaginal secretions from 13 patients with endometriosis. Antibody titres to endometrium (mean log2 +/- s.e.m., 7.08 +/- 0.80; P less than 0.0001), ovary (3.58 +/- 0.87; P = 0.0092), theca cells (4.42 +/- 0.73; P less than 0.0001) and granulosa cells (3.33 +/- 0.63; P = 0.0024) were significantly higher in the patients' sera than in sera from 15 normal non-pregnant females. Antibody titres to granulosa cells were elevated (7.97 +/- 1.46; P = 0.0424) in their cervical secretions. Antibody titres to all tissues tested were similar in vaginal secretions of patients and controls. Immunofluorescent antibody assay of biopsied endometrial tissue and sera from the patients revealed the antibodies to be primarily IgG and IgA. The results suggest that autoantibodies to endometrium and ovary are present in patients with endometriosis.
Immunoglobulin E (IgE) levels and antisperm antibody titers were determined in samples of serum and seminal plasma from 25 fertile men (Group A), 18 infertile men without measurable immunity to sperm (Group B), and 42 infertile men autoimmune to sperm (Group C), and in samples of serum and cervical and vaginal secretions from 25 fertile women (Group D), 28 infertile women without measurable immunity to sperm (Group E), and 32 infertile women isoimmune to sperm (Group F). Among the men, IgE levels in the serum, measured in international units per milliliter, were elevated in Group C (230 +/- 41, mean +/- SEM) as compared with Groups B (94 +/- 33, P less than 0.05) and A (55 +/- 8, P less than 0.001). In contrast, IgE levels in the seminal plasma in Group C (180 +/- 44) were not significantly different from those in Group B (48 +/- 21), but were higher than those in Group A (8 +/- 2, P less than 0.05). In the women, serum IgE levels were higher (P less than 0.001) in Group F, with isoimmunity to sperm (472 +/- 55), than in Groups E (219 +/- 32) and D (76 +/- 16). Wives of autoimmune husbands had somewhat, though not significantly, higher serum IgE levels (406 +/- 55), than had wives of nonautoimmune husbands (247 +/- 97). These results provide evidence for an elevated IgE response in subjects with significantly elevated antisperm antibody titers.
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Evidence is presented for cross-reactivity between antigens on human sperm and T lymphocytes. In 25 infertile couples in which both the males and females had significant antisperm immunity, antibody (Ab) titers to thymocytes (mean +/- S.E.M. 159 +/- 4 and 72 +/- 14, respectively, in males and females), T cell lines CCRF-CEM (69 +/- 5 and 48 +/- 8) and HSB-2 (56 +/- 15) and 41 +/- 8), suppressor-enriched (TG) cells (26 +/- 6 and 66 +/- 28) and helper-enriched (TG-) cells (26 +/- 4 and 46 +/- 14) were significantly elevated, as compared with Ab titers in 45 normal males and 45 normal females without antisperm immunity. Antibody titers to adult B cells, B cell line RAJI, and granulocytes were similar in the two groups. Antisperm Ab titers in sera, sperm extracts, and seminal plasma of the infertile subjects were significantly reduced after absorption with sperm, thymocytes, or T cell line CCRF-CEM but not with the B cell line RAJI. Antithymocyte Ab titers in the sera were significantly reduced (p less than 0.001) after absorption with thymocytes, CCRF-CEM, or sperm, but not RAJI. Lymphocytes from the infertile patients, when stimulated with pokeweed mitogen in vitro, produced antisperm and anti-T-lymphocyte antibodies at significantly higher titers than normal controls.
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Sperm antibody (AB) titers, determined by passive hemagglutination and cytotoxicity assays, were found to be elevated in 62 males and 46 females of 103 couples with primary infertility; 15 males and 12 females of 25 couples with secondary infertility; 10 males and 8 females of 18 couples with histories of repeated abortion; 21 males and 17 females of 25 couples in which the husband had a history of prostatitis; and 29 males and 17 females of 38 couples in which the husband had oligospermia. Of the couples in which one or both partners had elevated sperm AB titers, only 4 achieved pregnancy: 3 from the group with secondary infertility, all of which ended in spontaneous abortions, and 1 in which the husband was oligospermic. This suggests an etiologic role of sperm immunity in infertility. Immunosuppressive treatment of autoimmune males with prednisone (15 mg/day for 3 weeks to 6 months) resulted in significant decreases in AB titers. Pregnancies were achieved by 9 of 25 couples after treatment (36%). The observed increase in pregnancy rate in the prednisone-treated versus untreated groups of couples with elevated sperm AB titers was significant (P less than 0.02).
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