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Increased frequency of autoantibodies in men with sperm antibodies*
Vol. 43, No. 3, Marc~4985 Printed. in U.SA.
FERTILITY AND STERILITY Copyright' 1985 The American Fertility Society .J'
Increased frequency of autoantibodies in men with sperm antibodies*
H. W. Gordon Baker, M.D., Ph.D. t:I: Gary N. Clarke, M.Sc.§ M. Patricia McGowan, B.Sc. (Hon.)11 S. Hoon Koh, B.Sc. (Hon.)§ Maurice N. Cauchi, M.D., Ph.D.§ Royal Women's Hospital, Medical Research Centre, Prince Henry's Hospital,. and Howard Florey Institute of Experimental Physiology and Medicine, Melbourne, Victoria, Australia
Autoantibodies to thyroid microsomes were more frequent in 102 infertile men with complement-dependent sperm-immobilizing activity (sperm immobilization test [SIT]) in serum (11.8%) than: in a control group of 277 men of comparable ages and semen quality without sperm antibodies (4.3%, P < 0.05). Frequencies of organ-specific antibodies (antigastric parietal cell, antithyroglobulin, and antithyroid microsome) in 57 men with genital tract obstructions and positive SIT were similar to those for control subjects, and there were no significant differences in the frequencies of nonorgan-specific autoantibodies (antinuclear antibody, rheumatoid factor, antimitochondrial, and anti-smooth muscle) in the three groups. Because in men without genital tract obstruction antithyroid microsomal autoantibodies were more common with sperm antibodies than without, the possibility of a genetic factor in the causation of sperm autoimmunity should be considered. Fertil Steril 43:438, 1985
Sperm antibodies appear in many men after vasectomy and in some with other forms of obstructive azoospermia, presumably as a result of immunization via lymphatic or other systemic absorption of sperm antigens. 1 -4 Sperm autoimmunity also occurs in other men without genital tract obstructions for unknown reasons. In our infertility clinics, - 6% of men have complement-
Received July 2, 1984; revised and accepted October 26, 1984. *Supported by the National Health and Medical Research Council of Australia. tReprint requests: Dr. H. W. G. Baker, Medical Research Centre, Prince Henry's Hospital, St. Kilda Road, Melbourne, 3004 Victoria, Australia. :j:Howard Florey Institute of Experimental Physiology and Medicine, Parkville. *Department of Pathology and Reproductive Biology Unit, Royal Women's Hospital. IIReproductive Biology Unit, Royal Women's Hospital. 438
Baker et al.
Sperm antibodies and autoantibodies
dependent sperm-immobilizing activity in serum, detected by the sperm immobilization test (SIT).5 These men appear to have family histories of autoimmune diseases more often than other infertile men. 5 To investigate this association between sperm autoimmunity and other autoimmune phenomena further, we have determined the frequency of autoantibodies in the sera of men known to have sperm antibodies and compared them with those in sperm antibody-negative control subjects and patients with positive SIT and genital tract obstruction.
MATERIALS AND METHODS SUBJECTS
All subjects were being investigated for infertility. Those with positive SIT results were dividFertility and Sterility
ed into two groups: tG2- men 23 to 49 years of age (mean, 32 yea~·with ~ontaneously occurring" sperm antibodies and 57 men 27 to 46. years of age (mean, 36 years) with either epididymal·obstruc~ tions (13) or persisting infertility after attempted vasectomy reversal (44). A control group of 277 men with infertility and negative SIT results were selected because of similar age range (22 to 52· years of age; mean, 32 years) and semen quality to the first group. The men in the first, "spontaneous," SIT-p.ositive group and the control group had oligospermia (28%, mean sperm concentration < 20 million/ml), asthenospermia (59%, mean sperm concentration> 20 million/ml, mean motility < 60%), or normal semen analyses (13%); there were none with azoospermia. AUTOANTIBODY TESTS
The tests were performed on serum either fresh or after storage at - 20°C. The SIT was performed according to the World Health Organization recommendations, as previously described. 6 , 7 In this test the final dilution of serum is 1:2. All positive tests were confirmed in additional serum samples. The autoantibodies-antinuclear, antimitochondrial, anti-smooth muscle, and antigastric parietal cell-were detected by indirect immunofluorescence by the method of NairnB with minor modifications. Cryostat sections (4 /J.m) were obtained from composite blocks of mouse liver, stomach, and kidney, snap-frozen in liquid nitrogen-isopentane. The sections were· overlaid with serum diluted 1:5 in 0.1 M phosphate-buffered saline (PBS), pH 7.1, for 25 minutes at 20°C. Excess serum was removed by washing in two changes of PBS for 15 minutes. Fluorescein-conjugated rabbit antiserum to human immunoglobulins (Wellcome Diagnostics, Beckenham, England) was applied to the sections and incubated
and washed as· aWne:The sectiOns· were mottnted in PBS containing· 100/0. glycerol and examined with a Leitz· DiaIux: 20 EB fluorescence micro· seope(Leitz, Frankfurt, West Germany). The. intensity ofstaining was scored as negative or positive. The tests were performed in batches of 40 to 60 test sera with SIT-positive and SIT-negative samples in approximately a 1:2 ratio but not identifiable by the observer. Known positive and negative control sera and PBS background fluorescence controls were· also included in each batch. The thyroid autoantibodies anti microsomal and anti thyroglobulin were tested with Thymune M and Thymune Tkits,respectively, according to the manufacturer's·instructions (Wellcome Diagnostics). Rheumatoid factor· was also detected with a commercial kit (RapiTex-RF, Behringwerke AG, Marburg, West Germany). Chi-square tests were used to estimate the significance of differences between proportions. RESULTS
The number of subjects in each of the three groups found to have autoantibodies in their Sera is shown in Table 1. There was a significantly higher frequency of thyroid microsomal antibodies and organ-specific autoantibodies, as a group, in the men with positive SIT results than in the control group. Those with genital tract obstructions had results not significantly different from those for the control group. DISCUSSION
Sera from patients with sperm antibodies have been tested for other autoantibodies previously, and the frequency of positive tests was not higher than expected, but only small numbers were test-
Table 1. Frequency of Positive Autoantibody Tests in Infertile Men With and Without Sperm Immobilizing Activity in Serum Group
SIT·positive (spontaneous) (n = 102) SIT-negative (controls) (n = 277) SIT-positive (postobstruction) (n = 57)
ANA
RF
AM
ASM·
8 7.8% 13 4.7% 3 5.3%
0 0% 5 1.8% 1 1.8%
1 1.0% 0 0% 0 0%
7 6.9% 30 10.8% 4 7.0%
Autoantibody" AGPC ATG
5 4.9'7c 13 4.7% 2 3.5%
5 4.9% 3 1.1% 2 3.5%
ATM
OS
NOS
ANY
12b 11.8% 12 4.3% 3 5.3%
19b 18.6% 24 8.7% 6 1O.5'7c
16 15.7% 47 17.0% 8 14.0%
33 32.4% 66 23.8'7c 13 22.8%
aANA, antinuclear antibody; RF; rheumatoid factor; AM, antimitochondrial antibody; ASM,. anti-smooth muscle antibody; AGPC, antigastric parietal cell antibody;ATG, antithyroglobulin antibody; ATM, antithyroid microsomal antibody; OS, organspecific autoantibodies (AGPC, ATG, ATM); NOS, non-organ-specific autoantibodies (ANA, RF, AM, ASM); ANY, anyone or more autoantibodies positive. bp < 0.05 (chi-square test, compared with the control group). Vol. 43, No.3, March 1985
Baker et al. Sperm antibodies and autoantibodies
439
ed. 9, 10 In the present study, with a larger number of subjects and carefully aged-matched control subjects, the increase in prevalence of autoantibodies in men with positive SIT results was only statistically significant for thyroid microsomal antibodies. However, with even larger numbers of subjects, other autoantibodies (e.g., antithyroglobulin and antinuclear) might also be significantly more frequent than in control subjects. The prevalence of positive tests in the control group is similar to that reported by others for healthy men of the same age range, except for anti-smooth muscle antibodies, which appear to be more frequent (10.8%) than in other reportsY-13 A similar high frequency of anti-smooth muscle antibodies was reported by Donat and Morenz. 14 The possibility that smooth muscle antibodies may develop in men with infertility for other reasons requires further study. The results for men with genital tract obstructions and positive SIT results were not significantly different from those for control subjects. Most previous studies of vasectomized men have also shown no increased incidence of autoantibodies apart from those to sperm. 13, 15, 16 The only exceptions have been the reports of Mathews et al. 12 and Lucas and Rose,17 who found slightly increased frequencies of autoantibodies after vasectomy. Some hereditary aspects of development of sperm antibodies after vasectomy have also been suggested from findings of more frequent family histories of autoimmune diseases17 and human leukocyte antigen (HLA) A28 18 in sperm antibody-positive subjects. In men without evidence of specific events leading to sperm immunization, genetic predisposition to form sperm antibodies is, as in other autoimmune diseases,19 suggested by a rising incidence of sperm antibodies with age,20 clustering of sperm or testicular autoimmunity with other autoimmune diseases in the patient or in close relatives,5, 21 and linkage to histocompatibility antigens sueh as HLA B7;22 There is also an animal model in which organ-specific autoimmune lesions develop in mice if thymectomy is performed on day 3 of life. 23 These lesions include thyroiditis, gastritis, epididymitis, and orchitis. The affected mice have sperm antibodies in their serum and are infertile. It is suggested that thymectomy at this age prevents the development of a set of suppressor T cells which would usually inhibit proliferation of autoreactive immunocytes. The present finding of an increased preva440
Baker et al. Sperm antibodies and autoantibodies
lence of organ-specific autoantibodies in men with sperm antibodies without evidence of genital tract obstructions further supports the operation of genetic predisposition in the genesis of sperm autoimmunity. Acknowledgment. We wish to thank Mrs. Jill Volfsbergs for her secretarial assistance.
REFERENCES 1. Fjallbrant B: Interrelation between high levels of sperm antibodies, reduced penetration of cervical mucus by spermatozoa, and sterility in men. Acta Obstet Gynecol Scand 47:102, 1968 2. Friberg J: Serum and seminal immunoglobulins in relation to testicular morphology. J Androl 1:133, 1980 3. Sotolongo JR: Immunological effects of vasectomy. J Urol 127:1063, 1982 4. Linnet L: Clinical immunology of vasectomy and vasovasostomy. Urology 22:101, 1983 5. Baker HWG, Clarke GN, Hudson B, McBain JC, McGowan MP, Pepperell RJ: Treatment of serum autoimmunity in men. Crin Reprod Fertil 2:55, 1983 6. Rose NR, Hjort T, Riimke P, Harper MJK, Vyazov 0: Techniques for detection of iso- and autoantibodies to human spermatozoa. Clin ImmunoI23:175, 1976 7. Clarke GN, Stojanoff A, Cauchi MN, McBain JC, Speirs AL, Johnston WIH: Detection of anti-spermatozoal antibodies of IgA class in cervical mucus. Am J Reprod 1m· munol 5:61, 1984 8. Nairn RC: Fluorescent Protein Tracing, Fourth edition, Edinburgh, Churr.hill Livingstone, 1976, p 376 9. Wall JR, Stedronska J, David RD, Harrison RF, Goriup D, LessofMH: Immunologic studies of male infertility. Fertil Steril 26:1035, 1975 10. Boettcher B, Hjort T, Riimke P, Shulman S, Vyazov OE: Auto- and isoantibodies to antigens of the human reproductive system. I. Results of an international comparative study of antibodies to spermatozoa and other antigens detected in serum from infertile patients deposited in the WHO reference bank for reproductive immunology. Acta Pathol Microbiol Immunol Scand [e] (Suppl) 25:81, 1977 11. Whittingham S, Irwin J, Mackay IR, Marsh S, Cowling DC: Autoantibodies in healthy subjects. Aust Ann Med 18:130, 1969 12. Mathews JD, Skegg DCG, Vessey MP, Konice M, Holborow EJ, Guillebaud J: W"Elak autoantibody reactions to antigens other than sperm after vasectomy. Br Med J 2:1359, 1976 13. Bullock JY, Gilmore LL, Wilson JD: Autoantibodies following vasectomy. J Urol 118:604, 1977 14. Donat H, Morenz J: Autoantibodies in infertile couples. In Immunology of Reproduction, Proceedings of the Fifth International Symposium. Varna, Bulgaria, Bulgarian Academy of Sciences Press, 1982, p 300 15. Crewe P, Dawson L, Barnes RD, Tidmarsh E, Chanarin I, Hjort T, Ingerslev J: Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasect()my. Int J Fertil 22:104, 1977
Fertility and Sterility
16. Samuel T, Rose NR: The lessons of vasectomy-a review. J Lab Immunol 3:77, 1980 17. Lucas PL, Rose NR: Immunological consequences of vasectomy. I. Prospective study through I-year post-vasec- . tomy. Arch Androl 1:249, 1978 18. Law HY, Bodmer WF, Mathews JD, Skegg DCG: The immune response to vasectomy and its relation to the HLA system. Tissue Antigens 14:115, 1979 19. Mackay IR, Burnet FM: Autoimmune Diseases: Pathogenesis, Chemistry and Therapy. Springfield, IL, Charles C. Thomas, 1963 20. Fjallbrant B: Autoimmune human sperm antibodies and age in males. J Reprod Fertil 43:145, 1975
Vol. 43, No.3, March 1985
21. Murthy GG, Peress NS, Kahn SA: Demonstration of antibodies to testicular basement membrane by immunofluorescence in a patient with multiple primary endocrine deficiencies. J Clin Endocrinol Metab 42:637, 1976 22. Mathur S, Genco PV, Williamson HO, Koopman WR Jr, Rust PF, Fudenberg HH: Association of human leukocyte antigens B7 and BW35 with sperm antibodies. Fertil Steril 39:343, 1983 23. Taguchi 0, Nishizuka Y: Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol 46:425, 1981
Baker et al. Sperm antibodies and autoantibodies
441
FERTILITY AND STERILITY Copyright' 1985 The American Fertility Society .J'
Increased frequency of autoantibodies in men with sperm antibodies*
H. W. Gordon Baker, M.D., Ph.D. t:I: Gary N. Clarke, M.Sc.§ M. Patricia McGowan, B.Sc. (Hon.)11 S. Hoon Koh, B.Sc. (Hon.)§ Maurice N. Cauchi, M.D., Ph.D.§ Royal Women's Hospital, Medical Research Centre, Prince Henry's Hospital,. and Howard Florey Institute of Experimental Physiology and Medicine, Melbourne, Victoria, Australia
Autoantibodies to thyroid microsomes were more frequent in 102 infertile men with complement-dependent sperm-immobilizing activity (sperm immobilization test [SIT]) in serum (11.8%) than: in a control group of 277 men of comparable ages and semen quality without sperm antibodies (4.3%, P < 0.05). Frequencies of organ-specific antibodies (antigastric parietal cell, antithyroglobulin, and antithyroid microsome) in 57 men with genital tract obstructions and positive SIT were similar to those for control subjects, and there were no significant differences in the frequencies of nonorgan-specific autoantibodies (antinuclear antibody, rheumatoid factor, antimitochondrial, and anti-smooth muscle) in the three groups. Because in men without genital tract obstruction antithyroid microsomal autoantibodies were more common with sperm antibodies than without, the possibility of a genetic factor in the causation of sperm autoimmunity should be considered. Fertil Steril 43:438, 1985
Sperm antibodies appear in many men after vasectomy and in some with other forms of obstructive azoospermia, presumably as a result of immunization via lymphatic or other systemic absorption of sperm antigens. 1 -4 Sperm autoimmunity also occurs in other men without genital tract obstructions for unknown reasons. In our infertility clinics, - 6% of men have complement-
Received July 2, 1984; revised and accepted October 26, 1984. *Supported by the National Health and Medical Research Council of Australia. tReprint requests: Dr. H. W. G. Baker, Medical Research Centre, Prince Henry's Hospital, St. Kilda Road, Melbourne, 3004 Victoria, Australia. :j:Howard Florey Institute of Experimental Physiology and Medicine, Parkville. *Department of Pathology and Reproductive Biology Unit, Royal Women's Hospital. IIReproductive Biology Unit, Royal Women's Hospital. 438
Baker et al.
Sperm antibodies and autoantibodies
dependent sperm-immobilizing activity in serum, detected by the sperm immobilization test (SIT).5 These men appear to have family histories of autoimmune diseases more often than other infertile men. 5 To investigate this association between sperm autoimmunity and other autoimmune phenomena further, we have determined the frequency of autoantibodies in the sera of men known to have sperm antibodies and compared them with those in sperm antibody-negative control subjects and patients with positive SIT and genital tract obstruction.
MATERIALS AND METHODS SUBJECTS
All subjects were being investigated for infertility. Those with positive SIT results were dividFertility and Sterility
ed into two groups: tG2- men 23 to 49 years of age (mean, 32 yea~·with ~ontaneously occurring" sperm antibodies and 57 men 27 to 46. years of age (mean, 36 years) with either epididymal·obstruc~ tions (13) or persisting infertility after attempted vasectomy reversal (44). A control group of 277 men with infertility and negative SIT results were selected because of similar age range (22 to 52· years of age; mean, 32 years) and semen quality to the first group. The men in the first, "spontaneous," SIT-p.ositive group and the control group had oligospermia (28%, mean sperm concentration < 20 million/ml), asthenospermia (59%, mean sperm concentration> 20 million/ml, mean motility < 60%), or normal semen analyses (13%); there were none with azoospermia. AUTOANTIBODY TESTS
The tests were performed on serum either fresh or after storage at - 20°C. The SIT was performed according to the World Health Organization recommendations, as previously described. 6 , 7 In this test the final dilution of serum is 1:2. All positive tests were confirmed in additional serum samples. The autoantibodies-antinuclear, antimitochondrial, anti-smooth muscle, and antigastric parietal cell-were detected by indirect immunofluorescence by the method of NairnB with minor modifications. Cryostat sections (4 /J.m) were obtained from composite blocks of mouse liver, stomach, and kidney, snap-frozen in liquid nitrogen-isopentane. The sections were· overlaid with serum diluted 1:5 in 0.1 M phosphate-buffered saline (PBS), pH 7.1, for 25 minutes at 20°C. Excess serum was removed by washing in two changes of PBS for 15 minutes. Fluorescein-conjugated rabbit antiserum to human immunoglobulins (Wellcome Diagnostics, Beckenham, England) was applied to the sections and incubated
and washed as· aWne:The sectiOns· were mottnted in PBS containing· 100/0. glycerol and examined with a Leitz· DiaIux: 20 EB fluorescence micro· seope(Leitz, Frankfurt, West Germany). The. intensity ofstaining was scored as negative or positive. The tests were performed in batches of 40 to 60 test sera with SIT-positive and SIT-negative samples in approximately a 1:2 ratio but not identifiable by the observer. Known positive and negative control sera and PBS background fluorescence controls were· also included in each batch. The thyroid autoantibodies anti microsomal and anti thyroglobulin were tested with Thymune M and Thymune Tkits,respectively, according to the manufacturer's·instructions (Wellcome Diagnostics). Rheumatoid factor· was also detected with a commercial kit (RapiTex-RF, Behringwerke AG, Marburg, West Germany). Chi-square tests were used to estimate the significance of differences between proportions. RESULTS
The number of subjects in each of the three groups found to have autoantibodies in their Sera is shown in Table 1. There was a significantly higher frequency of thyroid microsomal antibodies and organ-specific autoantibodies, as a group, in the men with positive SIT results than in the control group. Those with genital tract obstructions had results not significantly different from those for the control group. DISCUSSION
Sera from patients with sperm antibodies have been tested for other autoantibodies previously, and the frequency of positive tests was not higher than expected, but only small numbers were test-
Table 1. Frequency of Positive Autoantibody Tests in Infertile Men With and Without Sperm Immobilizing Activity in Serum Group
SIT·positive (spontaneous) (n = 102) SIT-negative (controls) (n = 277) SIT-positive (postobstruction) (n = 57)
ANA
RF
AM
ASM·
8 7.8% 13 4.7% 3 5.3%
0 0% 5 1.8% 1 1.8%
1 1.0% 0 0% 0 0%
7 6.9% 30 10.8% 4 7.0%
Autoantibody" AGPC ATG
5 4.9'7c 13 4.7% 2 3.5%
5 4.9% 3 1.1% 2 3.5%
ATM
OS
NOS
ANY
12b 11.8% 12 4.3% 3 5.3%
19b 18.6% 24 8.7% 6 1O.5'7c
16 15.7% 47 17.0% 8 14.0%
33 32.4% 66 23.8'7c 13 22.8%
aANA, antinuclear antibody; RF; rheumatoid factor; AM, antimitochondrial antibody; ASM,. anti-smooth muscle antibody; AGPC, antigastric parietal cell antibody;ATG, antithyroglobulin antibody; ATM, antithyroid microsomal antibody; OS, organspecific autoantibodies (AGPC, ATG, ATM); NOS, non-organ-specific autoantibodies (ANA, RF, AM, ASM); ANY, anyone or more autoantibodies positive. bp < 0.05 (chi-square test, compared with the control group). Vol. 43, No.3, March 1985
Baker et al. Sperm antibodies and autoantibodies
439
ed. 9, 10 In the present study, with a larger number of subjects and carefully aged-matched control subjects, the increase in prevalence of autoantibodies in men with positive SIT results was only statistically significant for thyroid microsomal antibodies. However, with even larger numbers of subjects, other autoantibodies (e.g., antithyroglobulin and antinuclear) might also be significantly more frequent than in control subjects. The prevalence of positive tests in the control group is similar to that reported by others for healthy men of the same age range, except for anti-smooth muscle antibodies, which appear to be more frequent (10.8%) than in other reportsY-13 A similar high frequency of anti-smooth muscle antibodies was reported by Donat and Morenz. 14 The possibility that smooth muscle antibodies may develop in men with infertility for other reasons requires further study. The results for men with genital tract obstructions and positive SIT results were not significantly different from those for control subjects. Most previous studies of vasectomized men have also shown no increased incidence of autoantibodies apart from those to sperm. 13, 15, 16 The only exceptions have been the reports of Mathews et al. 12 and Lucas and Rose,17 who found slightly increased frequencies of autoantibodies after vasectomy. Some hereditary aspects of development of sperm antibodies after vasectomy have also been suggested from findings of more frequent family histories of autoimmune diseases17 and human leukocyte antigen (HLA) A28 18 in sperm antibody-positive subjects. In men without evidence of specific events leading to sperm immunization, genetic predisposition to form sperm antibodies is, as in other autoimmune diseases,19 suggested by a rising incidence of sperm antibodies with age,20 clustering of sperm or testicular autoimmunity with other autoimmune diseases in the patient or in close relatives,5, 21 and linkage to histocompatibility antigens sueh as HLA B7;22 There is also an animal model in which organ-specific autoimmune lesions develop in mice if thymectomy is performed on day 3 of life. 23 These lesions include thyroiditis, gastritis, epididymitis, and orchitis. The affected mice have sperm antibodies in their serum and are infertile. It is suggested that thymectomy at this age prevents the development of a set of suppressor T cells which would usually inhibit proliferation of autoreactive immunocytes. The present finding of an increased preva440
Baker et al. Sperm antibodies and autoantibodies
lence of organ-specific autoantibodies in men with sperm antibodies without evidence of genital tract obstructions further supports the operation of genetic predisposition in the genesis of sperm autoimmunity. Acknowledgment. We wish to thank Mrs. Jill Volfsbergs for her secretarial assistance.
REFERENCES 1. Fjallbrant B: Interrelation between high levels of sperm antibodies, reduced penetration of cervical mucus by spermatozoa, and sterility in men. Acta Obstet Gynecol Scand 47:102, 1968 2. Friberg J: Serum and seminal immunoglobulins in relation to testicular morphology. J Androl 1:133, 1980 3. Sotolongo JR: Immunological effects of vasectomy. J Urol 127:1063, 1982 4. Linnet L: Clinical immunology of vasectomy and vasovasostomy. Urology 22:101, 1983 5. Baker HWG, Clarke GN, Hudson B, McBain JC, McGowan MP, Pepperell RJ: Treatment of serum autoimmunity in men. Crin Reprod Fertil 2:55, 1983 6. Rose NR, Hjort T, Riimke P, Harper MJK, Vyazov 0: Techniques for detection of iso- and autoantibodies to human spermatozoa. Clin ImmunoI23:175, 1976 7. Clarke GN, Stojanoff A, Cauchi MN, McBain JC, Speirs AL, Johnston WIH: Detection of anti-spermatozoal antibodies of IgA class in cervical mucus. Am J Reprod 1m· munol 5:61, 1984 8. Nairn RC: Fluorescent Protein Tracing, Fourth edition, Edinburgh, Churr.hill Livingstone, 1976, p 376 9. Wall JR, Stedronska J, David RD, Harrison RF, Goriup D, LessofMH: Immunologic studies of male infertility. Fertil Steril 26:1035, 1975 10. Boettcher B, Hjort T, Riimke P, Shulman S, Vyazov OE: Auto- and isoantibodies to antigens of the human reproductive system. I. Results of an international comparative study of antibodies to spermatozoa and other antigens detected in serum from infertile patients deposited in the WHO reference bank for reproductive immunology. Acta Pathol Microbiol Immunol Scand [e] (Suppl) 25:81, 1977 11. Whittingham S, Irwin J, Mackay IR, Marsh S, Cowling DC: Autoantibodies in healthy subjects. Aust Ann Med 18:130, 1969 12. Mathews JD, Skegg DCG, Vessey MP, Konice M, Holborow EJ, Guillebaud J: W"Elak autoantibody reactions to antigens other than sperm after vasectomy. Br Med J 2:1359, 1976 13. Bullock JY, Gilmore LL, Wilson JD: Autoantibodies following vasectomy. J Urol 118:604, 1977 14. Donat H, Morenz J: Autoantibodies in infertile couples. In Immunology of Reproduction, Proceedings of the Fifth International Symposium. Varna, Bulgaria, Bulgarian Academy of Sciences Press, 1982, p 300 15. Crewe P, Dawson L, Barnes RD, Tidmarsh E, Chanarin I, Hjort T, Ingerslev J: Lack of association of the development of anti-sperm antibodies and other autoantibodies as a consequence of vasect()my. Int J Fertil 22:104, 1977
Fertility and Sterility
16. Samuel T, Rose NR: The lessons of vasectomy-a review. J Lab Immunol 3:77, 1980 17. Lucas PL, Rose NR: Immunological consequences of vasectomy. I. Prospective study through I-year post-vasec- . tomy. Arch Androl 1:249, 1978 18. Law HY, Bodmer WF, Mathews JD, Skegg DCG: The immune response to vasectomy and its relation to the HLA system. Tissue Antigens 14:115, 1979 19. Mackay IR, Burnet FM: Autoimmune Diseases: Pathogenesis, Chemistry and Therapy. Springfield, IL, Charles C. Thomas, 1963 20. Fjallbrant B: Autoimmune human sperm antibodies and age in males. J Reprod Fertil 43:145, 1975
Vol. 43, No.3, March 1985
21. Murthy GG, Peress NS, Kahn SA: Demonstration of antibodies to testicular basement membrane by immunofluorescence in a patient with multiple primary endocrine deficiencies. J Clin Endocrinol Metab 42:637, 1976 22. Mathur S, Genco PV, Williamson HO, Koopman WR Jr, Rust PF, Fudenberg HH: Association of human leukocyte antigens B7 and BW35 with sperm antibodies. Fertil Steril 39:343, 1983 23. Taguchi 0, Nishizuka Y: Experimental autoimmune orchitis after neonatal thymectomy in the mouse. Clin Exp Immunol 46:425, 1981
Baker et al. Sperm antibodies and autoantibodies
441