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Objectives: To evaluate the impact of autoantibodies against the M2-muscarinic receptor (anti-M2-R) on the clinical outcomes of patients receiving the standard treatment for peripartum cardiomyopathy (PPCM)., Methods: A total of 107 PPCM patients who received standard heart failure (HF) treatment between January 1998 and June 2020 were enrolled in this study. According to anti-M2-R reactivity, they were classified into negative (n = 59) and positive (n = 48) groups, denoted as the anti-M2-R (-) and anti-M2-R (+) groups. Echocardiography, 6-min walk distance, serum digoxin concentration (SDC), and routine laboratory tests were performed regularly for 2 years. The all-cause mortality, cardiovascular mortality, and rehospitalisation rate for HF were compared between the two groups., Results: A total of 103 patients were included in the final data analysis, with 46 in the anti-M2-R (+) group and 57 in the anti-M2-R (-) group. Heart rate was lower in the anti-M2-R (+) group than in the anti-M2-R (-) group at the baseline (102.7 ± 6.1 bpm vs. 96.0 ± 6.4 bpm, p < 0.001). The initial SDC was higher in the anti-M2-R (+) group than in the anti-M2-R (-) group with the same dosage of digoxin (1.25 ± 0.45 vs. 0.78 ± 0.24 ng/mL, p < 0.001). The dosages of metoprolol and digoxin were higher in the anti-M2-R (-) patients than in the anti-M2-R (+) patients (38.8 ± 4.6 mg b.i.d. vs. 27.8 ± 5.3 mg b.i.d., p < 0.0001, respectively, for metoprolol; 0.12 ± 0.02 mg/day vs. 0.08 ± 0.04 mg/day, p < 0.0001, respectively, for digoxin). Furthermore, there was a greater improvement in cardiac function in the anti-M2-R (-) patients than in the anti-M2-R (+) patients. Multivariate analysis identified negativity for anti-M2-R as the independent predictor for the improvement of cardiac function. Rehospitalisation for HF was lower in the anti-M2-R (-) group, but all-cause mortality and cardiovascular mortality were the same., Conclusions: There were no differences in all-cause mortality or cardiovascular mortality between the two groups. Rehospitalisation rate for HF decreased in the anti-M2-R (-) group. This difference may be related to the regulation of the autonomic nervous system by anti-M2-R., (© 2021. The Author(s).)

Objective: To describe 2 cases from a single academic institution of improvement in stiff-person syndrome (SPS) symptoms during pregnancy and to review the clinical outcomes of SPS in 6 additional pregnancies described in the literature., Methods: Evaluation of clinical symptoms and treatment changes of disease state during pregnancy., Results: Seven patients with 9 pregnancies are described in women with a diagnosis of SPS. Six of 7 (86%) women were positive for glutamic acid decarboxylase (GAD65) antibody. In 5 of 9 (56%) pregnancies, symptomatic medications (antispasmodics) were significantly reduced with stabilization or improvement in symptoms through pregnancy. Nine live, healthy pregnancies resulted. All 7 (100%) women experienced worsening of symptoms after the birth of their children, and symptomatic therapies were resumed and/or increased., Conclusions: The immune pathogenesis of SPS continues to be explored. Immunomodulatory shifts during pregnancy may influence changes of clinical SPS symptoms and provide insight into the unique pathogenesis of SPS. Some women with SPS may be able to reduce symptomatic medications related to clinical improvement during pregnancy. Women with SPS may safely carry pregnancies to term, delivering healthy and unaffected babies., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.)

Autoimmune lymphoproliferative syndrome (ALPS) is caused by germline or somatic loss of function FAS mutations resulting in impaired apoptosis and consequent expansion of T-lymphocytes causing organomegaly and autoimmune anemia, neutropenia and thrombocytopenia. Herein, we report on a case of disseminated varicella zoster infection after post-partum vaccination in a patient found to have CD4 lymphopenia and eventually diagnosed with ALPS caused by a novel germline missense mutation in FAS death-domain. A subsequent retrospective analysis of 169 patients of the NIH ALPS-FAS cohort, revealed that CD4-T-cells lymphopenia (< 300 cells/μl) may occur in 5% of ALPS-FAS patients irrespectively of the underlying genetic defect, organomegaly or immunosuppressive treatment. Although immunophenotyping did not show depletion of specific CD4-T-cells subpopulations, CD4-lymphopenic ALPS-FAS subjects had an expansion of a subset of circulating T-follicular-helper (cTfh) cells, associated with autoantibody production (CCR7 low PD-1 high ). Furthermore, autoantibodies binding on CD4-T-cells were detected in 50% of the CD4-lymphopenic ALPS-FAS patients and caused cytotoxicity in a natural killer (NK)-mediated antibody-dependent-cellular cytotoxicity assay. Such autoantibodies can therefore be associated with CD4-T-cell death, impaired activation induced proliferation or impaired trafficking. The expansion of autoreactive T-cells in ALPS-FAS is known to be associated with autoimmune clinical manifestations, however our study reveals that ALPS-FAS can also be associated with a paradoxical depletion of CD4-T-cells due to the presence of autoantibodies on the surface of CD4-T-cells which can in turn result in increased susceptibility to opportunistic infections. These novel findings have implications for the diagnosis, clinical monitoring, and management of patients with ALPS-FAS.

Preeclampsia (PE) is a poorly understood pregnancy complication. It has been suggested that changes in the maternal immune system may contribute to PE, but evidence of this remains scarce. Whilst PE is commonly experienced prepartum, it can also occur in the postpartum period (postpartum PE-PPPE), and the mechanisms involved are unknown. Our goal was to determine whether changes occur in the maternal immune system and placenta in pregnancies complicated with PE and PPPE, compared to normal term pregnancies. We prospectively recruited women and collected blood samples to determine the circulating immune profile, by flow cytometry, and assess the circulating levels of inflammatory mediators and angiogenic factors. Placentas were collected for histological analysis. Levels of alarmins in the maternal circulation showed increased uric acid in PE and elevated high-mobility group box 1 in PPPE. Analysis of maternal immune cells revealed distinct profiles in PE vs PPPE. PE had increased percentage of lymphocytes and monocytes whilst PPPE had elevated NK and NK-T cells as well. Elevated numbers of immune cells (CD45+) were detected in placentas from women that developed PPPE, and those were macrophages (CD163+). This work reveals changes within the maternal immune system in both PE and PPPE, and indicate a striking contrast in how this occurs. Importantly, elevated immune cells in the placenta of women with PPPE strongly suggest a prenatal initiation of the pathology. A better understanding of these changes will be beneficial to identify women at high risk of PPPE and to develop novel therapeutic targets.

Hypertension and inflammation during pregnancy are suggested to contribute to the development of postpartum depression and anxiety. Using a rat model of severe preeclampsia and hemolysis, elevated liver enzymes, and low platelet count syndrome, which displays both hypertension and inflammation during pregnancy, we evaluated whether rats were prone to develop depression or anxiety in the postpartum period. On gestational day 12, miniosmotic pumps infusing sFlt-1 (soluble fms-like tyrosine kinase-1) and sEng (soluble endoglin) were placed into rats, a subset of these rats was infused with 2 mg/kg of Orencia (abatacept) the following day to determine whether immune suppression via T-cell depletion prevented any changes in maternal depression or anxiety-like behavior. All rats, including normal pregnant (NP) controls, delivered between gestational days 21 and 22. Postpartum severe preeclamptic rats buried significantly more marbles compared with NP rats ( P=0.002) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats spent significantly more time in closed arms of the elevated plus maze compared with NP rats ( P=0.009) and Orencia-treated rats ( P=0.05). Severe preeclamptic rats were hypertensive compared with NP ( P=0.03) and Orencia-treated rats ( P=0.01). Finally, severe preeclamptic rats had increased blood-brain barrier permeability compared with NP rats ( P=0.03), which was reversed in Orencia-treated rats ( P=0.008). These results suggest that severe preeclampsia/hemolysis, elevated liver enzymes, and low platelet count syndrome during pregnancy contributes to an increase in anxiety-like behavior, blood-brain barrier permeability, and hypertension in the postpartum. The current results suggest that T-cell suppression during pregnancy can also help prevent chronic hypertension and increased anxiety in the postpartum period.

IgG4-related lung disease (IgG4-RLD) is recently emerging entity. Several reports concerned with the clinicopathologic feature have been described, but this disease in puerperium has not been reported previously. Here, we report a 24-year-old woman diagnosed as IgG4-RLD in puerperium, who developed dry cough, low fever and exertional dyspnea following the delivery. The inflammatory markers and pulmonary lesions of the patient suggested pneumonia. However, there was no improvement after antibiotic treatment. The infiltration of IgG4-positive lymphoplasmacytes was found in lung biopsy by video-assisted thoracic surgery (VATS). And the serum IgG4 level was high. The patient was effectively treated with corticosteroids. This unique case highlights the occurrence of IgG4-RLD in puerperium and underscores it should be taken into consideration as a possible differential diagnosis when dense lymphoplasmacytic infiltration was found in pulmonary consolidation in complex puerperal respiratory cases.

Up to half of dairy cows are affected by at least one of metritis, purulent vaginal discharge, endometritis or cervicitis in the postpartum period. These conditions result from inadequate immune response to bacterial infection (failure to clear pathogenic bacteria from the uterus) or persistent inflammation that impairs rather than enhances reproductive function. The degree of mobilization of fat and how effectively it is used as a metabolic fuel is well recognized as a risk factor for metabolic and infectious disease. Release of non-esterified fatty acids has direct effects on liver and immune function but also produces pro-inflammatory cytokines (tumor necrosis factor α and interleukin-6), which contribute to systemic inflammation and to insulin resistance. Therefore, reproductive tract inflammatory disease may be a function of both local and systemic inflammatory stimuli and regulation as well as regulation of fat metabolism. Better understanding of variables associated with insulin resistance and inflammatory regulation in the liver and adipose tissue may lead to improvement of reproductive tract health. This paper reviews factors that may contribute to postpartum reproductive tract inflammatory diseases in dairy cows and their inter-relationships, impacts and treatment.

Purpose: Test the hypothesis that puerperal mastitis may alter immunity related to the mucin (MUC) family of glycoproteins and lower risk of ovarian cancer., Methods: In two case-control studies conducted in New England between 1998 and 2008, we examined the association between self-reported mastitis and ovarian cancer in 1,483 women with epithelial ovarian cancer and 1,578 controls. IgG1 antibodies against (MUC1) CA15.3 and (MUC16) CA125 were measured using electrochemiluminescence assays in a subset of controls (n = 200). Preoperative CA125 was recorded in 649 cases. The association between ovarian cancer and mastitis was assessed using unconditional logistic regression to calculate adjusted odds ratios, OR, and 95 % confidence intervals (CI). Associations between mastitis and anti-CA15.3 and anti-CA125 antibodies and preoperative CA125 levels were evaluated using adjusted linear regression models., Results: Prior mastitis was associated with a significantly lower risk of ovarian cancer: OR (and 95 % CI) of 0.67 (0.48, 0.94) adjusted for parity, breastfeeding, and other potential confounders. The association was strongest with 2 or more episodes of mastitis, and risk declined progressively with increasing number of children and episodes of mastitis. Among controls, prior mastitis was associated with significantly higher anti-CA15.3 and anti-CA125 antibody levels and, among cases, with significantly lower preoperative CA125 levels., Conclusion: Puerperal mastitis may produce long-lasting anti-mucin antibodies that may lower the risk of ovarian cancer, plausibly through enhanced immune surveillance. Studying immune reactions related to MUC1 and MUC16 in the 10-20 % of breastfeeding women who develop mastitis may suggest ways to duplicate its effects through vaccines based on both antigens.

Peripartum myocardial infarction is a rare event that is associated with high mortality rates. The differential diagnosis includes coronary artery dissection, coronary artery thrombosis, vascular spasm, and stenosis. Our evaluation of 2 cases over a 5-year time period has led to a hypothesis that peripartum myocardial infarction is an immune-mediated event secondary to coronary endothelial sensitization by fetal antigen. In our patients, we supplemented standard medical therapy with immunotherapy consisting of corticosteroids, plasmapheresis, and intravenous immunoglobulin. Herein, we present our most recent case-that of a 29-year-old black woman (gravida V, para IV), 2 weeks postpartum with no relevant medical history. She presented with a 1-week history of chest pain. Initial electrocardiographic and cardiac biomarkers were consistent with acute coronary syndrome. Echocardiography revealed reduced systolic function with inferior-wall hypokinesis. Angiography revealed diffuse disease with occlusion of the left anterior descending coronary artery not amenable to revascularization. We were successful in treating the myocardial infarction without the use of catheter-based interventions, by modifying the immunologic abnormalities. Two cases do not make a protocol. Yet we believe that this case and our earlier case lend credence to the hypothesis that peripartum myocardial infarction arises from sensitization by fetal antigens. This concept and the immune-modifying treatment protocol that we propose might also assist in understanding and treating other inflammatory-disease states such as peripartum cardiomyopathy and standard acute myocardial infarction. All of this warrants further investigation.

Background: ADAMTS13-neutralizing IgG autoantibodies are the major cause of acquired thrombotic thrombocytopenic purpura (TTP)., Objective: To analyze the IgG subclass distribution of anti-ADAMTS13 antibodies and a potential relationship between subclass distribution and disease prognosis., Methodology: An enzyme-linked immunosorbent assay-based method was used to quantify the relative amounts of IgG subclasses of anti-ADAMTS13 antibodies in acquired TTP plasma., Results: IgG(4) (52/58, 90%) was the most prevalent IgG subclass in patients with acquired TTP, followed by IgG(1) (52%), IgG(2) (50%), and IgG(3) (33%). IgG(4) was found either alone (17/52) or with other IgG subclasses (35/52). IgG(4) was not detected in 10% of the patients. There was an inverse correlation between the frequency and abundance of IgG(4) and IgG(1) antibodies (P < 0.01). Patients with high IgG(4) levels and undetectable IgG(1) are more prone to relapse than patients with low IgG(4) levels and detectable IgG(1)., Conclusions: All IgG subclasses of anti-ADAMTS13 antibodies were detected in patients with acquired TTP, with IgG(4), followed by IgG(1), antibodies dominating the anti-ADAMTS13 immune response. Levels of IgG(4) could be useful for the identification of patients at risk of disease recurrence.

This experimental study aimed to evaluate the effect of relaxation techniques on anxiety levels, and the relation between anxiety and the concentration of Immunoglobulin A. The study was carried out in a maternity hospital in a city of the State of Espírito Santo, Brazil. The sample was composed of 60 puerperae. The information on the variables: age, education, marital status, type of childbirth, and parity were collected with a specific form; the trait and state of anxiety were based on the State Trait Anxiety Inventory (STAI/IDATE); and the level of salivary IgA was obtained through immunoturbidimetry. The application of the Mann-Whitney, Wilcoxon, and Pearson's correlation statistical tests showed a significant reduction in the levels of the state of anxiety in the experimental group (p = 0.01); there was no correlation between the trait and state variables of anxiety and the salivary IgA level; both groups (experimental and control) showed trait and state of medium-intensity anxiety.

Pregnancy is a state of subtle immunosuppression characterized by physiologic suppression of proinflammatory host responses that are meant to promote embryonic implantation. Rapid reversal of these changes and a rebound of inflammatory responses during the postpartum period can result in quiescent or latent infection manifesting as symptomatic disease. Infections due to several microbial pathogens and noninfectious diseases with an autoimmune basis have been shown to worsen or begin during the postpartum period. Awareness that symptoms resulting from immune reconstitution can occur in any host with a rapidly changing immunologic repertoire, including women in the postpartum phase, is a critical first step in fully understanding this phenomenon. Future studies to discern the precise pathophysiologic basis of immune reconstitution, to identify pregnant women at risk, and to determine markers that may be diagnostically helpful have significant implications for optimizing treatment of these patients.

Objective: To assess the relationship between mode of delivery and subsequent maternal HIV-1 disease progression., Design and Methods: Changes in CD4+ lymphocyte percentage (CD4%) and plasma HIV-1 RNA concentration (HIV RNA), and time to progression to AIDS or death among HIV-1-infected women were compared according to mode of delivery [cesarean section before labor and ruptured membranes (SCS), cesarean section after labor and/or after ruptured membranes (NSCS), and vaginal delivery]. Generalized estimating equations were used to compare changes in adjusted mean CD4% and HIV RNA counts by mode of delivery. Cox proportional hazard models were used to assess differences in time to AIDS or death., Results: In adjusted analyses, there were no clinically important differences in HIV-1 disease progression according to mode of delivery (SCS, n = 183; NSCS, n = 221; vaginal, n = 1087), as assessed by changes in CD4% and HIV RNA during the 18 months following delivery, and by progression to AIDS or death during a mean postpartum follow-up of 2.66 years., Conclusions: The present results suggest that, among HIV-1-infected women in North America, mode of delivery is not associated with subsequent HIV-1 disease progression.

Spontaneous coronary artery dissection (SCAD) is an extremely uncommon cause of myocardial infarction, occurring predominantly in women during or after pregnancy. The exact aetiology is unknown. This report describes a 33 year postpartum woman with diagnosed SCAD who tested positive for anticardiolipin antibody. This is the first case of SCAD in a patient with antiphospholipid antibody. The authors hypothesised that there should be a strong association between them.

Postpartum thyroid dysfunction (PPTD) develops during the first 9 months in up to 50% of women who have thyroid peroxidase antibodies (anti-TPOAb +ve). Humoral immunity in PPTD has been well documented, but the cellular immunological events accompanying the Th2 to Th1 state postpartum are less clear. Peripheral blood lymphocyte cytokine secretion was examined in 48 TPOAb +ve and 33 TPOAb -ve women at 36 wk gestation and at 6, 12, and 24 wk postpartum. Eighteen women with PPTD had significantly greater secretion of interferon gamma and IL-4 than euthyroid women at 36 wk gestation with no significant differences in cytokine secretion at other time points. Also, at 36 wk gestation, the median plasma cortisol concentration in the PPTD group was significantly lower than the euthyroid group (442 nmol/liter vs. 567 nmol/liter, P < 0.02). There were no differences between the groups in levels of prolactin, progesterone, or estradiol. These data suggest that there may be less immunological suppression at 36 wk in TPOAb +ve women destined to develop PPTD possibly because of lower levels of cortisol. Thus, the immunological determinants of PPTD may in part occur antenatally, although the mechanism(s) for this is still unclear.

Background: Postpartum thyroid dysfunction (PPTD) develops in 50% of pregnant women who have raised levels of circulating thyroid peroxidase autoantibodies (TPOAb) at booking. Although these antibodies are able to activate the complement cascade in vitro, it is not known whether complement activation plays any role in the pathogenesis of this disease., Aim: To investigate potential and actual activation of the complement system in women with postpartum thyroiditis., Design: Complement activation was monitored on a weekly basis in 24 postpartum women who had raised TPOAb at 16 weeks gestation, attending an antenatal clinic in Mid-Glamorgan, Wales., Methods: ELISA procedures were used to measure both in-vitro complement C3 activation by TPOAb and circulating terminal complement complexes (TCC) in serum., Results: Higher levels of bioactive TPOAb activity were seen in women who developed PPTD when compared to those who did not. However, TCC remained undetectable in serum throughout the period of study., Conclusions: In PPTD, despite the presence of circulating bioactive TPOAbs, the extent of complement activation is inadequate to cause detectable increases in peripheral blood TCC, suggesting that the complement system may not play a major role in PPTD pathogenesis.

Objective: To compare the cellular and humoral factors in colostrum from HIV infected and uninfected lactating mothers., Design: Cross sectional study., Setting: Maternity Ward., Methods: Colostrum was collected from 130 mothers (62 HIV seropositives and 68 HIV seronegatives). These colostrum samples were tested for total cell count, cell viability, differential count, phagocytic activity of macrophages, 'T' cell counts, IgA, IgM and IgG levels., Results: There was a statistically significant decrease in the phagocytosis and 'T' cell number (p <0.001) and in the IgA and IgG levels (p<0. 05) in the colostrum obtained from HIV seropositive mothers as compared to HIV seronegative ones., Conclusion: Some of the cellular and humoral factors are reduced in colostrum samples obtained from HIV seropositives as compared to normals.

Autoimmune diseases, especially autoimmune thyroid disease, frequently develop after delivery due to the immune rebound mechanism. Most cases have transient dysfunction of affected organs. Cardiac dysfunction developed after delivery is called postpartum or peripartum cardiomyopathy. However, the aetiology of the disease is not clarified yet. Here we report three cases that developed acute heart failure in the postpartum period. One was complicated with an atrioventricular block and postpartum autoimmune thyroiditis. All patients recovered to normal cardiac function or pre-attack condition after 1 month of therapy with conventional drugs and bed rest. All three had positive antiheart antibody detected by indirect immunofluorescence assay, and one had antibody to heart myosin detected by enzyme-linked immunosorbent assay. Moreover, one of two patients examined revealed lymphocytic infiltration by endomyocardial biopsy. Antibodies to 26 viruses were not elevated significantly during the first 2 weeks after admission in any case. It is strongly suggested that heart failure is induced by postpartum autoimmune myocarditis, and thus clinicians should be aware of this disease.

Objective: To investigate the prediction of the postpartum onset of rheumatoid arthritis (RA)., Methods: Two thousand five hundred and forty seven healthy pregnant subjects were examined prospectively and the relation between serum rheumatoid factors (RF) and postpartum onset of RA was observed. Rheumatoid factors were measured in early pregnancy by the antihuman IgG latex agglutination test (Latex test) and antirabbit IgG haemagglutination test (RAHA test)., Results: Latex test and RAHA test were positive in 26 (1.0%) and 64 (2.5%) pregnant subjects, respectively. Four hundred and ten subjects of 2547 pregnant women could be followed up for one year after delivery. None of 401 subjects without RF, or with only one RF on either Latex test or RAHA test, developed RA after delivery. Two (22.2%) of nine subjects with both RFs developed RA at one and three months postpartum, respectively. Transient arthralgia was found within 12 months postpartum in three of nine (33.3%) subjects with both RFs and this prevalence was significantly higher than that in RF negative subjects (8.1%)., Conclusion: Postpartum onset of RA was found in at least 2 of 2547 healthy subjects (0.08%) and onset was predicted by positive test for rheumatoid factors.

Postpartum (pp) thyroid dysfunction (PPTD) is thought to be caused by an autoimmune (AI) destruction of thyroid follicles during the pp period. The chronic thyroid AI process [already present in pregnancy, as shown by the positivity for thyroid peroxidase antibodies (TPO-Ab)] becomes overt disease in the pp period, and one assumes that this exacerbation represents a rebound phenomenon after a general immunosuppression during pregnancy. The presence of TPO-Ab in pregnancy has been suggested as a predictor for later PPTD development. Apart from B cells, e.g. production of autoantibodies, various functions of the cell-mediated immune (CMI) system, including those of peripheral T cells, monocytes, and dendritic cells (DC), are also disturbed in AI states. The objectives of the present study were: determining alterations in various CMI parameters in pregnancies followed by PPTD vs. those not followed by PPTD; and determining the usefulness of these parameters in the prediction of PPTD. In a prospective study (region: Kempenland, southeast Netherlands), a random sample of 291 women were tested at 12 and 32 weeks gestation and 4 weeks pp for TPO-Ab. Women were followed until 9 months pp, for developing PPTD. PPTD was defined as both: an abnormal TSH, and fT4 pp women developing PPTD and/or being positive for TPO-Ab (n = 26); and thyroidological uneventful control women of the same cohort, matched for age and parity (n = 21), were tested for thyroid-stimulating antibodies, percentages of peripheral blood lymphocyte subsets using fluorescence-activated cell sorter analysis (CD3, CD4, CD8, CD16, CD56, major histocompatibility complex-class II), for monocyte polarization, and for cluster capability of monocyte-derived DC. Results were: 1) 31 women (10.7%) were positive for TPO-Ab (TPO-Ab+) in gestation (12 and/or 32 weeks); 2) 15 women (5.2%) developed PPTD, of whom 10 were TPO-Ab+ in gestation; 3) pregnancy-related CMI alterations consisted of low percentages of CD16+CD56+ natural killer (NK), cells and a low DC cluster capability at 12 weeks gestation (these functions were normalized at 32 weeks gestation); 4) the TPO-Ab+ PPTD+ women (4 hyper, 5 hypo, and 1 hyper/hypo) were characterized by a persistently low percentage of NK cells, a lowered monocyte polarization, and a raised percentage of major histocompatibility complex-class II+CD3+ T cells; 5) the TPO-Ab- PPTD+ women (all 5 hyper) had neither thyroid-stimulating antibodies nor CMI alterations, apart from those normally seen in pregnancy; 6) 21 women were positive for TPO-Ab in pregnancy but did not develop PPTD (they had the same lowered NK cell percentages and monocyte polarization as the TPO-Ab+ PPTD+ cases, but they had normal percentages of activated peripheral T cells and a lower titer of TPO-Ab); 7) determination of the number of NK cells and monocyte polarization hardly contributed to the prediction of PPTD (as compared with TPO-Ab status), because of strong interindividual variation and close association with the presence of TPO-Ab; and 8) combining TPO-Ab assays with testing for activated T cells was the most optimal parameter for the prediction of TPO-Ab+ cases of PPTD in our small test set. We conclude that TPO-Ab+ pregnant women who develop PPTD show several CMI abnormalities other than those seen in normal pregnant women, such as persistently lower percentage of NK cells, a lowered monocyte polarization, and a raised percentage of activated T cells. The latter seems rather specific for the actual PPTD development and is not found in TPO-Ab+ (but PPTD) uncomplicated pregnancies. TPO-Ab- (but PPTD+) women had no signs of CMI abnormalities (apart from those specific for the pregnancy state). Although studied cases are low in number, our data are suggestive for the existence of two forms of PPTD: a TPO-Ab+ (AI) form (two-thirds of patients, classical PPTD pattern); and a TPO-Ab- (non-AI) form (one-third of patients, only hyper). Such assumption implies that, at best, two

Objective: To assess the relation between the course of rheumatoid arthritis (RA) during pregnancy or the onset of RA postpartum and DRB1, DQA1, and DQB1 incompatibilities between mother and child., Methods: In 45 pregnancies of 33 RA patients the course of RA was related to the number of class II incompatibilities. Furthermore class II incompatibilities in 16 pregnancies followed by RA onset were compared with those in 87 control pregnancies., Results: The risk of a favourable compared with an unfavourable course was 0.95, 2.67, and 2.38 in case of DRB1, DQA1, and DQB1 incompatibility respectively. DQA1 and DQB1 incompatibilities were seen more often in the 10 pregnancies followed by RA onset within three months than in control pregnancies (OR 8.02, 95% CI 0.97, 66.06 and OR 8.79 95% CI 1.07, 72.46 respectively)., Conclusions: DQA1 and DQB1 incompatibility between mother and child seems to have a favourable effect on the course of RA and may postpone the risk of RA onset during pregnancy.

The authors review the literature about peripartum cardiomyopathy and describe a case of a white woman, 31 years old, primipara, who developed myocardial failure six hours after caesarian operation, with good results after immunosuppressive therapy.

Differences in the levels of immune cell subsets present in peripheral blood have been demonstrated based on sociodemographic factors such as age and race. Postpartal women, who are recovering from the immune changes that are concomitant with pregnancy, have lymphocyte and monocyte values that differ from other populations. A subgroup of postpartal women, mothers who deliver preterm very-low-birth-weight (VLBW) (< or = 1,500 g) infants, may have further differences in values of immune cell subsets and in immune functioning either because of hormonal factors or lifestyle changes or because of the stress they experience after their infant's birth and for the first few months of infant caretaking. This study examined anxiety, depression, and immune cell phenotypes in 30 mothers of VLBW infants and in 30 mothers of healthy term infants over the first 4 postpartal months to determine if mothers of preterm VLBW infants differed from mothers of healthy term infants in psychological and immunologic parameters. Additionally, lymphocyte proliferation and natural killer cell functional assays were performed in a subset of mothers. Mothers of VLBW infants had increased anxiety and decreased lymphocyte proliferation compared to mothers of term infants. When lymphocyte and monocyte subsets were compared over time between the two groups of mothers differences were found in CD8, CD20, CD3-/CD56+, CD14, and HLA class II Ia on monocytes. Mothers with high-fat diets had lower percentages of some monocytes (CD14), lymphocytes (CD4+/CD45RA+), and natural killer cells (CD3-/CD57+) during the first 4 postpartal months.

Background: Postpartum thyroiditis (PPT), characterized by transient hyperthyroidism and transient hypothyroidism, occurs in 5-9% of women. It is accompanied by the presence of circulating antithyroid peroxidase antibodies (TPOAb) which have been associated with an increase in depressive symptomatology compared with TPOAb-negative women., Aim: To assess the frequency and nature of the syndrome in patients studied in detail after more than one pregnancy, as there are only sparse data on recurrence of PPT., Method: Fifty-four patients were identified who had participated in at least two of three detailed postpartum studies of thyroid and psychiatric function during the past 12 years in the Caerphilly and Cardiff regions of South Wales. They included two women who had had three pregnancies. All patients had been followed monthly postpartum for at least six months, and 44 had been followed for 12 months., Results: Of the 13 patients who developed PPT after their first pregnancy, nine had a recurrence of dysfunction after a further pregnancy and four remained TPOAb positive. Of the 24 women who were euthyroid anti-TPO positive after the first pregnancy, six developed thyroid dysfunction after a subsequent delivery, 14 remained antibody positive and euthyroid, while four underwent seroconversion and were antibody negative. The control group of 17 women were antibody negative after the first pregnancy; 16 remained negative after a further pregnancy and one became anti-TPO positive. The severity of PPT was slightly, but not significantly worse after the second recorded pregnancy (67% hypothyroid versus 44% hypothyroid). Neither the maximum anti-TPO titre following the first pregnancy, nor the rise in titre during this period were predictive of outcome after a subsequent pregnancy. Data from 26 women showed that recurrent depression was seen in 15.4%; a further six were depressed after the first pregnancy only, and two during a further postpartum period., Conclusion: There was a 70% chance of developing recurrent PPT after a first attack, and a 25% risk even in women who were only anti-TPO positive without thyroid dysfunction during the first postpartum period. The recurrence of postpartum depression was not related to thyroid function. Patients noted to have thyroid dysfunction or just to be euthyroid but anti-TPO positive after pregnancy should be assessed carefully after a subsequent pregnancy.

The clinical and biochemical features of postpartum thyroid disease were analysed in 152 antithyroid peroxidase antibody-positive (anti-TPO+ve) women and compared with 239 anti-TPO-ve age-matched control postpartum women. All were assessed monthly for up to 12 months postpartum. Seventy three anti-TPO+ve women developed postpartum thyroiditis (PPT): 19.2% hyperthyroid alone, 49.3% hypothyroid alone, and 31.5% characterized by hyper- followed by hypothyroidism. None of the antibody-negative women developed any thyroid dysfunction. A significant increase in many of eleven symptoms of hypothyroidism and some of eight symptoms of hyperthyroidism compared to control women was observed in all anti-TPO+ve women, independent of thyroid status. This was particularly seen in women who later developed PPT when they were euthyroid, but was also observed in euthyroid anti-TPO+ve women who showed no decline of thyroid function during the postpartum period. Although PPT is usually transient, this condition, and the euthyroid antibody-positive state, may be associated with significant symptomatology, including an increased incidence of minor to moderate depression. Early recognition of this syndrome by antenatal screening of thyroid antibodies may contribute to improved management of women during the postpartum period.

Mitogenic responses of peripheral blood lymphocytes in naturally occurring clinical puerperal metritis and mastitis were investigated. Glucose consumption index (GCI) values for phytohaemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM) in the puerperal metritic cows and mastitic cows were significantly lower than those in the healthy cows. Suppression of lymphocyte blastogenesis was correlated to an increased concentration of serum ammonia in the puerperal metritic cows, and of alpha 1-acid glycoprotein (alpha 1AG) in the mastitic cows. Lymphocyte blastogenesis in the mastitic cows was also correlated to the serum concentration of vitamin E. These findings indicate that the puerperal metritic and mastitic cows are associated with impaired lymphocyte blastogenesis.

A 28-year-old woman noticed a progressive gait disturbance after her first delivery. At the age of 32, the gait disturbance improved during her second pregnancy, but became worse after delivery and eventually resulted in a scissoring gait. At the age of 34, she became transiently thyrotoxic and was diagnosed as having painless thyroiditis and HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). The findings of this case suggest that the postpartum exacerbation of HAM/TSP was probably due to a rebound phenomenon after immunosuppression during pregnancy, and that the immunological abnormalities associated with HAM/TSP might have played some role in the development of painless thyroiditis.

The presence of autoimmune gastritis was investigated in 54 women with postpartum thyroiditis. Parietal cell antibodies (PCA) specific against H+, K(+)-adenosine triphosphatase (EC 3.6.1.36) were found in 18 women during pregnancy; in 10 of them, a 2-9-fold increase in the PCA level was observed in the postpartum period. At a 5-year follow-up, the initially PCA-positive women still had elevated antibody levels. Hypergastrinemia and low pepsinogen levels were noted in 4 women. In 2 of these women low serum vitamin B12 levels had developed. In 6 of 9 PCA-positive women examined by gastroscopy, biopsy specimens from the gastric body mucosa contained mononuclear cells, mainly T lymphocytes (CD3+) and macrophages (Leu-M3+) combined with an aberrant epithelial expression of HLA-DR. In four patients with chronic gastritis, all parietal cells, as defined by a specific monoclonal antibody, were found to have immunoglobulin G (IgG) deposits by a double-immunostaining method. Three of them had microscopic evidence of atrophy, whereas in 1 patient the body mucosa was intact. In 1 further patient with intact glands at histological examination, the basolateral membrane of some oxyntic glands was coated with IgG. The selective in situ deposition of antibodies associated with histologically intact parietal cells may support the concept that specific autoantibodies participate in the early pathogenesis of parietal cell destruction.

Objective: To define the relation between mood and autoimmune thyroid dysfunction during the eight months after delivery., Design: Double blind comparison of the psychiatric status of women positive and negative for thyroid antibodies. Clinical examination and blood sampling for free triiodothyronine and thyroxine, thyroid stimulating hormone, and thyroid antibody concentrations at four weekly intervals. Psychiatric assessment at six, eight, 12, 20, and 28 weeks post partum., Setting: Outpatient department of district hospital., Patients: 145 antibody positive women and 229 antibody negative women delivering between August 1987 and December 1989., Main Outcome Measures: Thyroid status. Number of cases of mental ill health by the general health questionnaire, research diagnostic criteria, Hamilton 17 item depression scale, hospital anxiety and depression scale, and Edinburgh postnatal depression scale., Results: Six weeks after delivery the general health questionnaire showed 62 (43%) antibody positive women and 65 (28%) antibody negative women had mental ill health (chi 2 = 8.18, p less than 0.005). Follow up of 110 antibody positive and 132 antibody negative women showed significantly greater depression by research diagnostic criteria in antibody positive women (47%) than antibody negative women (32%) regardless of thyroid dysfunction. Antibody positive women showed higher mean scores for depression on the Hamilton (6.01 v 3.89, p = 0.0002), Edinburgh (7.45 v 5.92, p = 0.031), and hospital depression scales (4.95 v 3.79, p = 0.003)., Conclusion: Depressive symptoms are associated with positive thyroid antibody status in the postpartum period.

Phytohemagglutinin (PHA) and concanavalin A (Con A)-induced blastogenesis of peripheral blood lymphocytes was examined in heat-stressed pre- and postpartal sheep. The peak responses of lymphocytes to PHA and Con A in heat-stressed sheep revealed significant reduction before and after parturition compared with those in the corresponding control animals kept under thermoneutral conditions. Furthermore, the effect of serum from control or heat-stressed sheep on PHA-induced lymphocyte blastogenesis was examined. Supplementation of serum from heat-stressed sheep significantly suppressed the blastogenesis of lymphocytes obtained from healthy sheep, bovine, and human donors. Unlike dexamethasone, heat-stressed sheep serum did not inhibit IL-2 production by PHA-stimulated human peripheral blood lymphocytes. These results indicate that the immunosuppression of heat-stressed sheep is in part mediated by serum factor(s) that can modulate T-cell function in a species nonspecific manner.

The potential role of thyroid microsomal (Mic) antibodies in the development of postpartum hypothyroidism was investigated in 34 euthyroid women, whose sera were found to contain Mic antibodies in pregnancy. Additional serum samples were obtained 2. 5 and 10-12 months after delivery and analysed for IgG class and IgG subclass levels of Mic antibodies by ELISA techniques. Characteristically, Mic antibodies decreased from early pregnancy to 2 months postpartum, increased two-fold 5 months postpartum and had returned 10-12 months postpartum to the early pregnancy level. Mic antibodies were predominantly subclass IgG-1 or IgG-4 with only minor contributions from IgG-2 and IgG-3. In each individual the percentage contribution made by each IgG subclass to Mic antibody was essentially similar in early pregnancy and the postpartum period despite changes in total IgG class Mic antibody. During the year following delivery, thyrotoxicosis alone (Graves' disease) developed in 5 women. In the remaining 29 patients the absolute levels of Mic antibodies of IgG-4 subclass were similar 5 months postpartum in women with maximal serum thyrotropin (TSH) greater than 20 mU/1 (mean optical density in ELISA +/- s.d.; 0.84 +/- 0.538; n = 13) and in women with maximal TSH less than 10 mU/l (0.69 +/- 0.457; n = 16). In contrast, significantly higher values were observed for Mic antibody of IgG-1 subclass in patients with TSH greater than 20 mU/l (1.14 +/- 0.440) compared with women with maximal TSH less than 10 mU/l (0.65 +/- 0.289) (P less than 0.001 by t-test for groups). These results imply that the magnitude of Mic antibody levels of subclass IgG-1 but not IgG-4 is associated with the development of postpartum hypothyroidism and possibly with tissue destruction in autoimmune thyroid disease in general.

At 22 hr after an uncomplicated delivery of a healthy full-term infant, a 26-year-old woman developed toxic-shock syndrome (TSS). A vaginal culture yielded a coagulase-positive Staphylococcus that produced staphylococcal enterotoxin F (SEF) but no other enterotoxins. Breast milk specimens obtained on postpartum days 5, 8, and 11 contained 3.0, 2.5, and 2.0 ng of SEF/ml, respectively. Sera obtained from the mother on postpartum days 4 and 38 had titers (by radioimmunoassay) of antibody to SEF of 1:5 and less than 1:5, a result demonstrating a persisting lack of antibody to SEF after the first episode of TSS; the infant's serum titer of antibody to SEF on day 38 was also less than 1:5. Further longitudinal monitoring of SEF and antibody to SEF in breast milk from this patient is presented. This case is the first isolation of SEF from a body fluid obtained from a patient with TSS further strengthens the association between SEF and TSS.

A high prevalence of postpartum thyroid dysfunction has been reported in several countries, but there have been no systematic studies of its prevalence in Britain. Among a group of 901 consecutive, unselected pregnant women thyroid autoantibodies were detected in 117 (13%) at booking. The clinical course of postpartum thyroid dysfunction, factors associated with its development, and its likely prevalence were defined in 100 of these women with thyroid antibodies and 120 women with no such antibodies who were matched for age. None of the women had a history of autoimmune thyroid disease. Normal reference ranges for thyroid function during pregnancy and post partum were established in the 120 women negative for thyroid antibodies. On the basis of these observations postpartum thyroid dysfunction was observed in 49 (22%) of the 220 women studied, and the prevalence in the total group of 901 women was estimated to be 16.7%. Thyroid dysfunction, mainly occurring in the first six months post partum, was usually transient and included both destruction induced hyperthyroidism and hypothyroidism. The development of the syndrome was significantly related to smoking more than 20 cigarettes a day and the presence of thyroid microsomal autoantibodies at booking. Of the 16 women with a family history of thyroid disease in whom thyroid microsomal autoantibody activity was detectable at booking, 11 developed thyroid dysfunction. Age, parity, presence of goitre at presentation, duration of breast feeding, and the sex and birth weight of the infant were not associated with the development of postpartum thyroid dysfunction. The mood changes experienced by women post partum may in part be associated with altered thyroid function during this time.

Since the advent of routine automated platelet counting we have observed unexplained periparturient thrombocytopenia (PPT) in an unexpected number of periparturient women, ie, during labor or within 24 hr postpartum. Mean +/- SD platelet count in 686 random blood donors was 236 +/- 50 X 10(9)/L and 1.02% had a platelet count less than 136 X 10(9)/L; in 2,204 random prenatal and postpartum women mean count was significantly higher (275 +/- 86 X 10(9)/L; p less than 0.001). Of 1,621 periparturient women, 74 (4.6%) had unexplained PPT (mean +/- SD platelet count 122 +/- 24 X 10(9)/L, range 21-135 X 10(9)/L, N = 74). Platelet count in PPT usually rose to normal within 1 week of delivery; in 10% thrombocytopenia persisted greater than 6 months. PPT occurred in successive pregnancies with normal intervening platelet counts. Nine of 34 newborns of mothers with PPT were thrombocytopenic; there was no correlation between mother's and baby's platelet counts. In no case of PPT was there excessive bleeding in mother or infant. Positive indirect platelet radioactive antiglobulin tests (PRAT) were seen in 11% of normal postpartum women and in 90% of 22 women with PPT; 65% of the positive tests in PPT were due to reactions with anti-C3 only. In contrast, pregnant women with autoimmune thrombocytopenic purpura (AITP) had positive PRAT primarily because of anti-IgG (+/- anti-C3); only 10% were positive only with anti-C3. Results were concordant in all of eight women with PPT tested by both indirect and direct PRAT. Amount of C3 bound per platelet in direct or indirect PRAT was not predictive of degree of thrombocytopenia, but there was correlation of fg C3 per platelet detected by the two assays in individual patients (r = 0.8). Mean levels of serum C3, C4, and factor B in women with PPT did not differ from normal; individual patients had abnormal serum complements but no characteristic pattern was observed. Increased immune complexes were observed in 6% of normal subjects and 33% of women with PPT. Etiology and mechanism of PPT is unclear. Despite lack of clinical evidence in women with PPT of syndromes associated with increased platelet destruction, the presence of preeclampsia cannot be absolutely excluded. Similarly, although the pattern of antiglobulin sensitization in PPT differed markedly from that seen in AITP, autoimmune disorder cannot be excluded. Alloantibodies did not appear to be responsible for PPT. While PPT is usually benign, some patients had a markedly reduced platelet count. Recognition of the phenomenon may be important in obstetrics.

The immunoregulatory mechanisms underlying the transient rebound of autoimmune disease activity in the postpartum period were studied by determining serum immunoglobulins, thyroid microsomal antibodies and some viral (cytomegalovirus, Epstein-Barr, varicellae-zoster and mumps) and bacterial (Yersinia enterocolitica and Salmonella) antibodies in women with autoimmune thyroiditis and in healthy postpartum women. A characteristic increase between 2 and 5 months postpartum followed by a decrease to 10-12 months postpartum was observed not only for thyroid microsomal antibody titres in women with autoimmune thyroiditis but also for serum total IgG and IgG subclass levels (but not IgM, IgA or IgE) in both groups of women. This pattern of transient antibody increase was not detected against viral and bacterial antigens. The characteristic alterations of thyroid microsomal antibody titres in the postpartum period of women with autoimmune thyroiditis thus appear to occur as a consequence of an activation of immunoglobulin-producing B cell clones. This activation seems restricted to the IgG class and to certain B cell clones.