Immunological studies in recurrent spontaneous abortion: effects of immunization of women with paternal mononuclear cells on lymphocytotoxic and mixed lymphocyte reaction blocking antibodies and correlation with sharing of HLA and pregnancy outcome

Smith, J. Bruce; Cowchock, F. Susan

doi:10.1016/0165-0378(88)90062-9

Cited by 84 publications

(32 citation statements)

References 18 publications

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“…Only 4 out of 120 women who had live births developed antibodies prior to 14 weeks' gestation. The lack of correlation of cytotoxic antibodies with pregnancy outcome post-immunization was also reported by other investigators [11,25]. However, others reported that cytotoxic antibodies are predictive of favorable pregnancy outcome [8][9][10].…”

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confidence: 51%

Paternal Leukocyte Immunization in Primary Recurrent Spontaneous Aborters

1993

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This was a pilot study to investigate the possible roles of human lymphocyte antigen (HLA), antipaternal lymphocytotoxic antibodies, and maternal antipaternal mixed lymphocyte reaction (MLR) blocking antibodies in the maintenance of pregnancy following paternal leukocyte immunization for patients with recurrent abortions. A total of 36 patients with unexplained, first trimester, primary recurrent spontaneous abortions were investigated for the detection of these two antibodies. There was a 43.3% rate of discordance in the presence of the two antibodies (P <0.05). A total of 26 of these women who lacked either antibody were immunized with paternal leukocytes on two occasions and the assays were repeated postimmunization. The seroconversion rate was 50% for lymphocytotoxic antibodies and 61.5% for maternal serum (MLR) blocking antibodies. Twenty patients achieved pregnancies postimmunization, 11 completed their pregnancies successfully, and 9 re-aborted. A total of 83.3% of patients who developed MLR blocking antibodies post-immunization had successful pregnancies while those who failed to seroconvert aborted again. This difference is statistically significant (P <.05). A total of 50% of patients who developed lymphocytotoxic antibodies post-immunization had successful pregnancies while only 40% who failed to seroconvert reaborted. This difference, we felt, was not statistically significant. The development of MLR blocking antibodies post-immunization is a better indicator of subsequent successful pregnancies than lymphocytotoxic antibodies.AM Bahar, AG White, IH Al-Abdullah, Paternal Leukocyte Immunization in Primary Recurrent Spontaneous Aborters. 1993; 13(2): 130-135 Certain instances of unexplained spontaneous abortions may be due to the failure of immunological recognition and adaptation to the fetoplacental unit. The precise nature of this interaction is not completely understood; however, one feature may be the failure of the fetus to stimulate in the mother protective antibodies that alter antigen expression as well as promote growth of the trophoblast [1,2].Treatment by immunization with paternal or donor leukocytes to stimulate antibody production to leukocyte trophoblast crossreactive epitopes has been tried by different groups with encouraging results [3]. In these groups, the criteria for selection of patients for immunotherapy differ. One criterion is the sharing of HLA antigens [4]. There is evidence of increased antigen sharing between recurrently aborting women and their partners with sharing frequencies more than can be expected by chance alone [5][6][7]. Other criteria include the lack of paternal HLA lymphocytotoxic antibodies [8][9][10] or the lack of mixed lymphocytic reaction (MLR) blocking antibodies [11][12][13]. These antibodies are commonly present in the sera of normal multiparous women but found to be lacking in the sera of recurrently aborting women [14][15][16][17][18][19][20].The results of immunotherapy on successful pregnancy outcome using different criteria for selection are...

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confidence: 51%

Paternal Leukocyte Immunization in Primary Recurrent Spontaneous Aborters

1993

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“…1966;Mowbray et ai. 19S5;Takakuwa et ai, 1986), Others have found no correlation between pregnancy outcome and the presence of serum blocking activity, either before or after immunization (Gill, 1983;Smith &Cowchock, 1988), Somehavecastdoubt on the entire concept of circulating blocking faclors. because blocking activity often docs not appear until late in Ihe first or second trimester of the lirst pregnancy (Scolt et ai.…”

Section: Discussionmentioning

confidence: 99%

“…This has become a controversial area, and attempts lo ireat idiopathic recurrent spontaneous abortions with various immunotherapcutic regimens have generated a great deal of publicity (Slapsys & Clark, 1980: Mowbray et at., 1985Adinolfi. 1986;Takakuwa et ai, 1986;Hofmeyr et at.. 1987;Smith & Cowchock. 1988).…”

Section: Discussionmentioning

confidence: 99%

“…1985;Dayacr^;/., 1985). We(Caudal ct at.. 19S3) and others have found no correlation between the success of pregnancy and HLA histoincompatibility belween couples (Gill, 1983;Kilpatrick, 1984;Okscnbcrg el at., 1984;Beer (•/(//., 1985;Unander & Lindholm, 1986;Regan & Braude, 1987;Smith & Cowchock. 1988) or between the presence or absence of anli-patcrnal leucocytotoxic anlibodies (Zak & Good, 1959;Gill, 1983;Mowbray et at.. 1985;Smilh & Cowchock, 1988).…”

Section: Discussionmentioning

confidence: 99%

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Interpretation of blocking activity in maternal serum depends on the equation used for calculation of mixed lymphocyte culture results

Park

Edwin

Scott

et al. 1990

Clinical and Experimental Immunology

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SUMMARYImmunosLipprcssivc blocking factors in maternal serum arc usually determined by inhibition of mixed lymphocyte cultures (MLC), but reports on the importance of these factors for successful pregnancy are conflicting. Here we measured serum blocking activity in men. non-pregnant nullipiirous women, non-pregnant multiparous women, women with normal pregnancies, and in women who had had recurrent spontaneous abortions and were treated with leucocyte immunizations. Three ditferent equations were used for calculation of blocking activity: blocking effect index (BE!): stimulation index (SI); and blocking index (BI). By all three methods of calculation, significantly lower levels of blocking aetivity were noted for men and women compared with pregnant women and muttiparae. In the patients with a history ol' recurrent spontaneous abortions blocking activity as determined by BEI and BI increased into the positive range after treatment with infusions of third-party donor leucocytes in a statistically significant number of women {P<0-05). However. blocking activity as determined by BEI had a higher predictive value for successful pregnancy than did ihat determined by BI or SI. Our data suggest that Ihe equation used for ealculaling BEI is superior to other methods for the determination of blocking activity when monitoring the response to leucocyte immunization in women with recurrent spontaneous abortion. However, these results also cast doubt on the importance of blocking antibodies in histories of recurrent abortion, since pregnancies occurred in the absence and spontaneous abortions occurred in the presenee of blocking activity.

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“…Ранние исследования показали, что дефицит указанных антител у женщин с наличием в анам-незе ПНБ или беременных с угрозой выкидыша [2,4] ассоциируется с высоким сходством партне-ров по HLA-антигенам гистосовместимости [7,17,34]. Соответственно, для профилактики и ле-чения ПНБ был предложен метод иммунизации лимфоцитами отца, позволяющий индуцировать появление БФ [2,4] , Филиппинах 12 и др., однако однозначного мнения в отношении эф-фективности данного метода так и не сложилось.…”

Section: Introductionunclassified