James S. Scott

Connective-Tissue Disease, Antibodies to Ribonucleoprotein, and Congenital Heart Block

The relation between congenital heart block and maternal connective-tissue disease was studied by antibody screening of serum samples obtained in connection with 45 cases of isolated congenital complete heart block. Serum was available from 41 mothers (17 who had connective-tissue disease and 24 who were healthy) and 21 children. Thirty-four mothers had antibody to a soluble tissue ribonucleoprotein antigen called Ro(SS-A), which was identified by immunodiffusion. Anti-Ro(SS-A) was found in seven of eight serum samples collected from affected children when they were less than three months old but in none of 13 samples obtained when these children were older. It appears that maternal anti-Ro(SS-A) antibody crosses the placenta and is a marker for risk of congenital complete heart block; its absence from maternal serum suggests that a child is unlikely to be affected. Anti-Ro(SS-A) or a related antibody is probably involved in the pathogenesis of congenital complete heart block.

Maternal Antibodies against Fetal Cardiac Antigens in Congenital Complete Heart Block

An immunologic basis for congenital heart block has been proposed previously. To investigate the association between congenital heart block and maternal antibodies capable of crossing the placenta, we used immunofluorescence to examine serum samples from 41 mothers and 8 affected children, together with serum from controls, for antibodies to fetal cardiac tissue. Twenty-one mothers (51 percent) had IgG antibody reactive with fetal heart tissue, as compared with only 9 of 94 controls (10 percent; P less than 0.001). Three of 8 affected babies, but none of 50 healthy babies, had similar antibodies. The antibodies reacted with all myocardial tissue and were not directed specifically to the conduction system. They also reacted with other fetal tissues and could be distinguished from nuclear and smooth-muscle autoantibodies. We also observed a higher occurrence of antibodies to cytomegalovirus, but not to Epstein-Barr virus, in these mothers. Autopsy specimens from babies with congenital heart block examined by immunoperoxidase staining showed deposition of immunoglobulin and complement components in all cardiac tissues. These findings strengthen the case implicating immune reactivity related to maternal antibody in the development of some but not all cases of congenital heart block.

Presence of autoantibodies in women with unexplained infertility

Serum samples from 41 patients suffering from unexplained infertility and 351 normal pregnant women were assayed for a range of autoantibodies by means of immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion, Western blots, and enzyme-linked immunosorbent assays. The prevalence of autoantibodies to smooth muscle, phospholipid, and nuclear antigens, the latter when detected by immunofluorescence, was elevated in women with infertility compared with normal pregnant women (p less than 0.001, less than 0.001, and less than 0.05, respectively). Antiviral antibodies were not detected. The reason for the high level of autoreactivity in infertile women is unclear, but smooth muscle and antiphospholipid antibodies may actively interfere with the reproductive process.

Ovarian endocrine activity in association with hormonally inactive neoplasia

Abstract A case of ovarian carcinoma secondary to as gastric primary is recorded which was associated with hormone activity as judged by pre- and postoperative hormone assays. Elevation of pregnanediol excretion was the principal endocrine effect noted. In the light of the histologic findings and the recorded evidence it is concluded that ovarian stromal reaction of thecal type around the enlarging tumor is the mechanism producing such endocrine effects. The literature is reviewed in an attempt to discover a clue as to why some ovarian tumors produce this effect and not others. It is postulated that this phenomenon is basically a quantitative one related to the surface area of the neoplasm.

The Effect of Neonatal Exchange and Later Blood Transfusion on Lymphocyte Cultures

ABSTRACT: As blood transfusion has a beneficial effect on renal graft survival and may confer a protection against preeclampsia, the effect of neonatal or late blood transfusion on lymphocyte cultures was studied. Mixed lymphocyte reactions were significantly less even 20 years after transfusion.

Connective Tissue Disease Antibodies and Pregnancy

Half a century ago, the first hint that there might be such a subject as reproductive immunology came with Hench’s observation of the frequent improvement of rheumatoid arthritis (RA) in pregnancy, which led to discovery of cortisone and corticosteroid therapy. Twenty years later when organ transplant was being pioneered, the discipline developed as a recognizable entity, and it did so particularly in relation to the immunologic problem of the fetus as a graft. It was observed in women with connective tissue diseases (CTDs) that although antibodies such as lupus erythematosus (LE) factor and antinuclear factor crossed the placenta to their children, these did not produce any obvious disease. Consequently, CTDs were virtually ignored in the early years of reproductive immunology. In this period, however, pregnancy observations led to major advances in the elucidation of the mechanisms of a number of single-system autoimmune diseases, notably myasthenia gravis, thrombocytopenic purpura, and thyroid diseases.1

Suppression of Early Rhesus Sensitization by Passive Anti‐D Immunoglobulin:Suppression of Early Rhesus Sensitization

Anti‐D immunoglobulin is an effective prophylactic against rhesus isoimmunization. It is generally regarded as ineffective once antibody production has developed though there have been a number of inconclusive reports suggesting it may suppress early sensitization. Anti‐D (100μg) was given after delivery of a rhesus (D) positive child to a rhesus (D) negative mother who was shown to have anti‐D antibodies at that time by five tests on two separate specimens in two different laboratories and by a weakly positive direct anti‐globulin test on the cord blood. In a further pregnancy with a rhesus (D) positive child no antibody was detected by multiple tests including enzyme technique.

Congenital AV-block: Role of Anti-Ro and Anti-La Antibodies

ConclusionsIt seems fairly definite that the development of congenital AV block depends upon the transplacental passage of maternal autoantibody to the fetus. There is compelling evidence for the involvement of anti-Ro (SS-A)/La (SS-B) antibodies in this process, although the definitive pathogenic antibody may be a different, closely related, one. Anti-Ro (SS-A)/La (SS-B) antibodies are certainly markers for risk of occurrence of CCHB, since all mothers of babies born with such heart block possess these antibodies.There is at present no way of predicting which mothers with anti-Ro (SS-A)/La (SS-B) antibodies will have babies with CCHB. The risk of recurrence of heart block in a subsequent child of a women with one child with CCHB has been estimated as about one in four.Demonstration of anti-Ro (SS-A)/La (SS-B) antibodies in maternal serum should alert the clinician to both the likelihood of the later development of CTD in the woman, and the possibility of CCHB in the fetus/neonate. Echocardiography will help to confirm the diagnosis and facilitate the early institution of pacemaker therapy, if required.Increasing evidence that pathogenic events leading to AV block are related to autoantibody mechanisms opens up the possibility that it could be prevented by removal of the antibody from the maternal circulation or blocking its effect with an appropriate monoclonal or anti-idiotypic antibody.

Suppression of Early Rhesus Sensitization by Passive Anti-D Immunoglobulin

Anti-D immunoglobulin is an effective prophylactic against rhesus isoimmunization. It is generally regarded as ineffective once antibody production has developed though there have been a number of inconclusive reports suggesting it may suppress early sensitization. Anti-D (100 micrograms) was given after delivery of a rhesus (D) positive child to a rhesus (D) negative mother who was shown to have anti-D antibodies at that time by five tests on two separate specimens in two different laboratories and by a weakly positive direct anti-globulin test on the cord blood. In a further pregnancy with a rhesus (D) positive child no antibody was detected by multiple tests including enzyme technique.

Autoantibodies to soluble cellular antigens in unexplained recurrent abortion and infertility

In 36 women with unexplained primary recurrent abortion, 13 with secondary unexpained recurrent abortion, 25 with primary unexplained infertility, 7 with secondary unexplained infertility and two groups of control women, autoantibodies to soluble cellular antigens were measured by Western blotting to a disaggregated HeLa cell antigen preparation, by counter immunoelectrophoresis and by indirect immunofluorescence. Using Western blotting the women with primary infertility and those with secondary recurrent abortion had a significantly higher prevalence of autoantibodies (P less than 0.01 in each case). This was not shown using the other methods. It is possible that these antibodies could be causally related to the pathology of the conditions studied.