Pekka Kurki

Intravenous immunoglobulin treatment of Dregnant patients with recurrent pregnancy osses associated with antiphospholipid antibodies

The effects of high dose iv‐immunoglobulin on antiphospholipid antibody levels and on pregnancy outcome was studied in one patient with secondary (SLE) and two patients with primary antiphospholipid syndrome during their four pregnancies. These three women had had two pulmonary embolies related to pregnancy and estrogen containing pills, 13 miscarriages and only one liveborn after pre‐eclamptic pregnancy. During the four pregnancies the patients also received 75 mg of aspirin per day. Progressive depression of IgG‐anticardioli‐pin antibody titer was observed after repetitive high dose iv‐immunoglobulin (1 g/kg body‐weight) infusions. The effects on lupus anticoagulant were variable. Three pregnancies ended in a delivery of healthy child after 36‐38 weeks of gestation and one preterm child (34 weeks), with slight respiratory distress syndrome, was born. Our results support the idea that the addition of iv‐immunoglobulin to aspirin prophylaxis is worth considering when the patient has a severe antiphospholipid syndrome and/or is refractory to usual treatments.

Marker antibodies of rheumatoid arthritis: Diagnostic and pathogenetic implications

Rheumatoid arthritis (RA) is associated with several autoantibodies specific enough to serve as diagnostic and prognostic markers. These include rheumatoid factor (RF), antikeratin antibody (AKA), antiperinuclear factor (APF), and anti-RA33. The first three, and possibly also anti-RA33, may precede the onset of clinical RA. The prevalence of positive test reactions depends on the period between taking the specimen and onset of disease; when the period is short, the prevalence is nearly the same as in established disease. Thus, RA has a long asymptomatic period with broadening immunological activity. The assays for AKA and APF (and possibly also for anti-RA33), compared with RF testing, yielded greater specificity rather than the ability to define any subgroup with particularly severe disease. Used together, the above marker antibodies may form a new and more enlightened basis for defining seropositive RA. It is commonly believed that genetically mediated immune response plays an important role in the initiation of RA. However, the role of the major histocompatibility complex antigens may be in modulation of the inflammatory reaction in a later phase.

Autoantibody to “intermediate filaments” in infectious mononucleosis

Abstract By employing indirect immunofluorescent staining we detected autoantibodies against circulating lymphoblasts in the sera of two patients with acute infectious mononucleosis (IM). The target structures were identified as intermediate filaments (IMF) by their antigenic and biochemical properties. High titers of anti-IMF autoantibody were detected in 32 of 48 (67%) IM patient sera but not in control sera. The antibodies were usually of IgM class. The presence of anti-IMF antibodies did not correlate with anti-smooth muscle antibodies, and absorption studies revealed that the specificity of these antibodies differed from that of heterophilic (Paul-Bunnell) antibodies. The results may be interpreted as suggesting that the rapid turnover of lymphocytes in IM may be associated with a release of autoimmunogenic cytoplasmic intermediate(-sized) filaments.

A Solid Phase Enzyme‐linked Immunosorbent Assay (ELISA) for the Demonstration of Antibodies against Denatured, Single‐stranded DNA in Patient Sera

A solid phase enzyme‐linked‐immunosorbent assay (ELISA) for the determination of antibodies against denatured, single‐stranded (ss‐) DNA is described. Polystyrene cuvettes coated with ss‐DNA were incubated with serum samples and the anti‐ss‐DNA antibodies bound were detected by means of an anti‐IgG‐alkaline phosphatase conjugate. The binding of anti‐ss‐DNA antibodies in individual sera was expressed as units calculated as % of the absorbance in relation to the absorbance value obtained with a reference pool. Absorption experiments showed that the assay is specific for antibodies against denatured DNA. By using immunologically purified anti‐ss‐DNA antibodies the assay was shown Co detect specific antibodies in concentrations down to 1 ng/ml. Antibodies against DNA could be detected in 94% of sera with antinuclear antibodies.

Immune-mediated Congenital Heart Block (CHB): identifyingand counseling patients at risk for having children with CHB

OBJECTIVE To identify patterns of maternal antibodies associated with an increased risk of having a child with congenital heart block (CHB) and to provide a basis for counseling women with a previously affected child. METHODS This retrospective clinical study of the obstetric histories of 46 Finnish women with a CHB child compared the strength and specificity of the immune response to SS-A/Ro and SS-B/La, as determined by immunoblot and ELISA, in 44 affected women with 85 women with systemic lupus erythematosus (SLE) and 32 women with primary Sjögrens syndrome (SS) with healthy children. RESULTS High levels of anti-SS-A/Ro and anti-SS-B/La by practically all assays were associated with a significantly increased risk of having a CHB child. The best single test to identify high-risk mothers was anti-52 kd SS-A/Ro by immunoblot (OR 18.9), and it was the only assay to detect mothers at increased risk of CHB as compared with controls with primary SS. Low risk of CHB was indicated by undetectable or low levels of antibodies in the ELISA assays and no reactivity on immunoblot. Mothers with a previous child with CHB had a history of fetal loss (mostly spontaneous abortions) or a history of recurrent fetal losses (> or = 3) slightly more often than controls. Late-trimester obstetric complications in non-CHB pregnancies were insignificant. The relative risk for a female child compared with a male child to have CHB was 1.9 (1.2-2.9, P = .009), and the risk of the mother having another child with CHB was 12% (4 of 34). CONCLUSION Although there is no unique antibody profile specific for CHB, mothers with a high or low risk of having a child with CHB can be identified. Female children appear to have an increased risk of CHB, but the risk of the mother having another child with CHB is low.

Characterization of human smooth muscle autoantibodies reacting with cytoplasmic intermediate filaments.

Abstract Human smooth muscle antibodies (SMA) reacting with cytoplasmic intermediate filaments were characterized by the indirect immunofluorescence technique. These antibodies were noted to comprise a major type of SMA. When cultured human embrynic fibroblasts treated with a microtubulus-disrupting drug, vinblastine, were used, the SMA reacting with intermediate filaments (IMF-SMA), could be readily distinguished from other types of SMA by the immunofluorescence staining pattern. Absorption studies with intermediate filaments prepared from cultured human embryonic fibroblasts and from bovine smooth muscle tissue indicated that there are more than one autoantigen in the intermediate filaments of smooth muscle. The major subunit protein of intermediate filaments having a molecular weight of 55,000 was enriched in the antigenically active preparations of intermediate filaments. Five of 26 patients positive for IMF-SMA had signs of liver diseases and only two had chronic hepatitis.

Cellular fibronectin in rheumatoid synovium and synovial fluid : a possible factor contributing to lymphocytic infiltration

Mouse monoclonal antibodies against ED sequence‐containing cellular fibronectin (cFn) were used to show that Fn in the inflamed synovium is distinct from the major form of plasma Fn (pFn). An accumulation of cFn was seen at sites of hyperplasia of the rhcumatoid synovial membrane and in the walls of small vessels in the synovium by immunofluorescence microscopy. cFn was also found in rheumatoid synovial fluid by immunoblotting. Approximately one‐fifth of the T lymphocytes from rheumatoid synovial fluid bound to Fn, The binding of synovial fluid T cells was always higher than that from peripheral blood. These results have two implications. On the one hand, the cellular type of Fn may be an indicator of synovial inflammation. On the other hand, the deposition of Fn may be a factor contributing to the infiltration ol mononuclear cells into the synovium.

Smooth muscle antibodies of actin and “non-actin” specificity

Abstract The specificity and immunoglobulin class of smooth muscle antibodies (SMA) were studied in the sera of patients with urogenital cancer, acute respiratory infection, and chronic hepatitis and in the sera of blood donors by the indirect immunofluorescence technique (IFL). SMA activity could be neutralized with skeletal muscle actin in all 20 sera from patients with chronic hepatitis but in only 21 out of 57 other SMA-positive sera. The IFL staining patterns of anti-actin and anti-“non-actin” SMA were different; anti-actin antibodies reacted with the glomerular mesangia and I bands of myofibrils, whereas anti-“non-actin” antibodies reacted with the periphery of myofibrils and with intercalated discs. The specificity and diagnostic significance of SMA are discussed.

Determination of anti-actin antibodies by a solid-phase immunoenzymatic assay and by indirect immunofluorescence technique

Abstract Human anti-actin antibodies and experimental rabbit anti-actin antibodies of IgG-class were determined by enzyme-liked immunosorbent assay (anti-actin-ELISA) using actin from bovine skeletal muscle as antigen. The results were compared to those obtained by indirect immunofluorescence microscopy of anti-actin antibodies (anti-actin-IFL test). The anti-actin-ELISA proved to be suitable for quantitative determination of spontaneous and experimental anti-actin antibodies. The results of the anti-actin-ELISA test for human anti-actin antibodies correlated well with the results of the anti-actin-IFL test, although the anti-actin-ELISA may not detect all human anti-actin antibodies. Rabbits immunized with bovine skeletal muscle actin readily produced anti-actin antibodies detectable by the anti-actin-ELISA but only occasionally by the anti-actin-IFL test. The results show that human anti-actin antibodies react well with the “native” actin in tissue sections, whereas the experimental rabbit antibodies reacted well with “denatured” actin attached to the solid phase in the ELISA-assay but not with tissue sections. This indicates that there are different specificities of anti-actin antibodies.

Congenital heart block in one of the HLA identical twins

A case of HLA identical twins with one affected by congenital heart block is reported. Both twins, as their mother, had more than 12-fold higher anti-Ro antibody titers compared to healthy controls, but no differences were observed between the affected and the healthy baby. It is possible that there is a third factor causing the manifestation of this disease.