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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).)

Background: Longitudinally extensive transverse myelitis (LETM) accompanying systemic lupus erythematosus (SLE) is often due to coexisting aquaporin-4-IgG seropositive neuromyelitis optica spectrum disorder but has not been associated with myelin oligodendrocyte glycoprotein-IgG (MOG-IgG)., Objective and Methods: Case report at an academic medical center., Results: A 32-year-old woman developed severe transverse myelitis (paraplegia) shortly after SLE onset in the post-partum period. Magnetic resonance imaging (MRI) revealed an LETM, cerebrospinal fluid showed marked inflammation, and testing for infections was negative. Serum live-cell-based assay for MOG-IgG was positive but aquaporin-4-IgG was negative., Conclusion: In patients with SLE and LETM, MOG-IgG testing should be considered, in addition to AQP4-IgG.

Women may present with psychiatric disorders during pregnancy, normal labor, following delivery by caesarean section, or in the postpartum period. The accumulating evidence suggests that these disorders may be due to changes in immune responses. During pregnancy complications such as the prolongation of cervical ripening or descent, placental abruption, premature labor, and preeclampsia increase the risk of postpartum psychiatric disorders. Women may exhibit depression and postpartum psychosis following either normal birth or caesarean section. Since psychiatric disorders like schizophrenia, major depression, and bipolar disorder are associated with both alterations in the immune response and changes in immune cell subpopulations, in this study we have chosen to examine whether the psychiatric disorders in women during labor or postpartum also lead to aberrant immune responses.

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 diseases represent a complex heterogeneous group of disorders that occur as a results of immune homeostasis dysregulation and loss of self-tolerance. Interestingly, more than 80% of the cases are found among women at reproductive age. Normal pregnancy is associated with remarkable changes in the immune and endocrine signaling required to tolerate and support the development and survival of the placenta and the semi-allogenic fetus in the hostile maternal immune system environment. Gravidity and postpartum represent an extremely challenge period, and likewise the general population, women suffering from autoimmune disorders attempt pregnancy. Effective preconception counseling and subsequent gestation and postpartum follow-up are crucial for improving mother and child outcomes. This comprehensive review provides information about the different pathways modulating autoimmune diseases activity and severity, such as the influence hormones, microbiome, infections, vaccines, among others, as well as updated recommendations were needed, in order to offer those women better medical care and life quality., (Copyright © 2019. Published by Elsevier Ltd.)

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.

Background: Emerging evidence suggests a possible role for immune system dysregulation in the pathogenesis of postpartum psychosis (PP) but the evidence is limited. The current study sought to determine the serum cytokines/ chemokine changes associated with first-onset PP., Methods: Women with first onset PP were recruited as cases and the cytokines/ chemokine changes were compared against healthy postpartum (HP) and healthy non-postpartum (HNP) women.There were 20 subjects in each of the three groups. Levels of serum cytokines and Monocyte Chemoattractant Protein-1 (MCP-1) were estimated with a cytometric beadarray assay., Results: HP group showed significantly elevated levels of interleukin (IL)-6 as compared to HNP group. Whereas, the first onset PP group showed significantly elevated levels of both IL-6 and IL-8 as compared to HNP group., Conclusion: Postpartum period appears to be a state of altered immune functioning considering the elevated level of IL-6 in both HP and PP group. Additionally, IL-8 appears to play a role in the manifestation of PP. Our study highlights the immune alterations associated with first-onset PP., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Pregnancy is associated with a number of significant changes in maternal physiology. Perhaps one of the more notable changes is the significant alteration in immune function that occurs during pregnancy. This change in immune function is necessary to support a successful pregnancy, but also creates a unique period of life during which a female is susceptible to disease and, as we'll speculate here, may also contribute to mental health disorders associated with pregnancy and the postpartum period. Here, we review the known changes in peripheral immune function that occur during pregnancy and the postpartum period, while highlighting the impact of hormones during these times on immune function, brain or neural function, as well as behavior. We also discuss the known and possible impact of pregnancy-induced immune changes on neural function during this time and briefly discuss how these changes might be a risk factor for perinatal anxiety or mood disorders., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Background: Since postpartum psychosis has been linked to activation of the immune system, it has been hypothesized that infectious agents may be involved in the pathogenesis of this disorder. We therefore investigated whether exposure to pathogens that can infect the central nervous system is increased in patients with postpartum psychosis., Methods: We measured the prevalence and titers of immunoglobulin G (IgG) and M (IgM) to herpes simplex virus type 1 (HSV-1) and 2 (HSV-2), Epstein-Barr virus (EBV), cytomegalovirus (CMV) and Toxoplasma Gondii (TG) in a cohort of patients with postpartum psychosis (n = 81) and compared these to matched postpartum controls., Results: We did not find significant differences in seroprevalence or antibody titers for any of these pathogens., Limitations: Limitations of this study include the indirect measurement of infectious disease and the cross-sectional design., Conclusion: Our results do not support the hypothesis that exposure to these neurotropic pathogens is involved in postpartum psychosis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women., Background: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis., Methods: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of <0.45 within 2 months of delivery. Peripheral T-cell subsets, natural killer (NK) cells, and cellular activation markers were assessed by flow cytometry in PPCM women early (<6 wk), 2 months, and 6 months postpartum and compared with those of HP women and women with non-pregnancy-associated recent-onset cardiomyopathy (ROCM)., Results: Entry NK cell levels (CD3-CD56+CD16+; reported as % of CD3- cells) were significantly (P < .0003) reduced in PPCM (6.6 ± 4.9% of CD3- cells) compared to HP (11.9 ± 5%). Of T-cell subtypes, CD3+CD4-CD8-CD38+ cells differed significantly (P < .004) between PPCM (24.5 ± 12.5% of CD3+CD4-CD8- cells) and HP (12.5 ± 6.4%). PPCM patients demonstrated a rapid recovery of NK and CD3+CD4-CD8-CD38+ cell levels. However, black women had a delayed recovery of NK cells. A similar reduction of NK cells was observed in women with ROCM., Conclusions: Compared with HP control women, early postpartum PPCM women show significantly reduced NK cells, and higher CD3+CD4-CD8-CD38+ cells, which both normalize over time postpartum. The mechanistic role of NK cells and "double negative" (CD4-CD8-) T regulatory cells in PPCM requires further investigation., (Copyright © 2017 Elsevier Inc. All rights reserved.)

The aim was to determine the dynamic profile of interactions between Escherichia coli (E. coli) and the actions of leukotrienes (LTs) and TNF and INFγ (cytokines) in the uterus in vitro. Uterine explants (N=6) were incubated for 2, 12 and 24h either as E. coli-treated (10 6 CFU) or non-treated and/or with: LTB 4 and C 4 (10 -6 M, for both LTs), LTs receptors antagonists (aLTR; 10 -6 M) and/or cytokines (each 10ng/ml). Toll Like Receptor 4 (TLR4) mRNA expression increased in explants incubated with E. coli, cytokines and LTs after 2 and 12h and aLTR inhibited the effect of LTs in explants incubated with E. coli (P<0.05). IL-6 mRNA expression was up-regulated in E.coli-treated explants with cytokines after 2h and cytokines with LTs after 12h (P<0.05). E. coli increased prostaglandin (PG)E 2 output after all examined time points, and PGF 2α and IL-6 levels in E.coli-treated explants after 12 and 24h with cytokines, with LTs (P<0.05). aLTR inhibited LT stimulating action on PGs and IL-6 output in explants incubated with E. coli after 12 and 24h (P<0.05). LTs modify and enhance experimentally induced infection: TLR4 and IL-6 mRNA expression, IL-6 and PGs secretion, and cytokines participate in this process., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Objective: Significant immunological alterations have been observed in women with first-onset affective psychosis during the postpartum period. Recent studies have highlighted the possibility that a subset of patients with first-onset severe psychiatric episodes might suffer from undiagnosed autoimmune encephalitis. Therefore, the authors performed a three-step immunohistochemistry-based screening for CNS autoantibodies in a large cohort of patients with postpartum psychosis and matched postpartum comparison subjects., Method: Ninety-six consecutive patients with postpartum psychosis and 64 healthy postpartum women were included. Screening for antibodies in patient serum was performed using immunohistochemistry. Samples showing any staining were further examined by immunocytochemistry using live hippocampal neurons and cell-based assays to test for anti-N-methyl-d-aspartate (NMDA) receptor antibodies. Cell-based assays for all other known CNS antigens were performed in those samples with immunocytochemistry labeling but negative for NMDA receptor antibodies., Results: Four patients (4%) with neuropil labeling suggestive for extracellular antigen reactivity were identified. Serum samples from all four patients showed clear extracellular labeling of live hippocampal neurons. Two women had the specific staining pattern characteristic for anti-NMDA receptor antibody positivity, which was confirmed by cell-based assays. Neither patient with anti-NMDA receptor antibody positivity had evidence of an ovarian teratoma. The other two patients tested negative by cell-based assays for all known CNS antigens. None of the matched postpartum comparison subjects had confirmed neuronal surface antibodies. The two patients with anti-NMDA receptor antibodies both showed extrapyramidal symptoms following initiation of treatment with low-dose haloperidol., Conclusions: In patients with acute psychosis during the postpartum period, systematic screening for anti-NMDA receptor autoantibodies should be considered. The acute onset of severe atypical psychiatric symptoms in young female patients should raise the index of suspicion for anti-NMDA receptor encephalitis, particularly in the setting of neurological symptoms, including extrapyramidal side effects of antipsychotic treatment.

Problem: Little is known about postpartum immune recovery and relationships of common dysphoric moods, stress, immunology, and endocrinology., Method of Study: Healthy women (n = 72) were followed for six postpartum months with immune and hormone measures and dysphoric moods and stress scales. A panel of cytokines produced in mitogen-stimulated whole blood assays were measured at each time, along with plasma levels of hsC-reactive protein (hsCRP), Interleukin-6 (IL-6), and a panel of hormones., Results: Cellular immunity, measured by production of Interferon-gamma (IFNγ) and (Interleukin-2 (IL-2) from stimulated whole blood culture, was low in the early postpartum with changes by 3 months. Tumor necrosis factor alpha (TNFα) showed a similar pattern. Plasma levels of CRP and Interleukin-6 (IL-6) showed higher levels in the early postpartum. Mood disturbance scores dropped across the postpartum with a change in slope at 3 months. No significant relationships were found between immune, endocrine, and psychosocial measures., Conclusion: Return to normal cellular immune function may take 3-4 months in the postpartum. Some aspects of early immunology (hsCRP and IL-6) probably reflect the latter stage of pregnancy, the stress of birth and the inflammation associated with involution. Dysphoric moods are higher in the early postpartum but are not related to immune factors or hormones., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

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.

This paper reviews puerperal metritis in the cow, particularly the complex and multi-factorial pathogenesis characterized by an altered cross-talk among infectious agents, endocrine and immune systems. Uterine infections impair fertility and is one of the main causes of economic losses in dairy production. The early postpartum is a period characterized by an increased exposition to infectious agents and the disruption of the metabolic homeostasis, leading to endocrine and immunologic disorders. Dysregulation of uterine defence mechanisms results in the development of metritis. Because there is a complex interaction between infectious, endocrine and immune factors during metritis, there is need to use safer and cheaper drugs which are able to strengthen the anti-infective actions of the routine therapies.

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.

Post-partum uterine disease has a detrimental effect on dairy cow fertility; affected cows require more serves per conception, have reduced conception rates and are more likely to be culled for infertility. Furthermore, the detrimental effects on fertility remain even after clinical resolution of disease. There are many factors that influence a cow's resistance to or development of post-partum disease, and the key drivers determining disease outcome are uterine microbial load, regulation of inflammation and immune responses peripherally and at a local level, production pressure, and metabolic (energy) status. These factors are intricately interlinked, which makes assessment of their individual effects difficult. It is clear, however, that the period surrounding calving is a key transition phase and events during this time point will influence uterine disease outcome and subsequent fertility. Good peripartum management and accurate diagnosis are critical to facilitate the use of the most effective treatment and limit the negative impact of post-partum uterine disease on fertility. If we can improve our understanding of the underlying causes of disease, then we can identify 'at risk' animals and implement management and breeding strategies to prevent uterine disease or reduce its severity. Thus, this article aims to summarize the key factors that drive uterine disease in the post-partum dairy cow., (© 2013 Blackwell Verlag GmbH.)

Objective: The effects of low maternal hemoglobin levels on the immunological and nutritional components of breast milk at different maturation stages were investigated., Methods: Colostrum, transitional and mature milk were collected from 25 mothers with normal hemoglobin levels (control group) and 18 mothers with hemoglobin levels below 11 g/dL (anemia group). Total protein, antibodies, complement proteins, fat and calorie, lipase, iron, transferrin levels, total iron-binding capacity, latent iron-binding capacity (LIBC) and transferrin saturation index (TSI) were determined., Results: In contrast to the control group, anemic mothers had higher total protein levels in milk, lower IgA and IgG levels in colostrum, lower C3 protein levels in milk, lower C4 protein levels in colostrum and transitional milk, higher fat in the colostrum and lower calorie content in mature milk. In both groups, lipase was lower in mature milk and iron concentration was similar. Transitional and mature milk from anemic mothers had higher LIBC and lower TSI values., Conclusion: A decrease in maternal hemoglobin levels causes immunological and nutritional alterations in milk at different maturation stages. Special measures must therefore be taken for mothers at risk of developing anemia to ensure they can provide high-quality milk to their babies.

The incidence and severity of disease in cows is greatest during the transition period, when immune functions are impaired. Intense lipid mobilization is associated with both metabolic and infectious diseases in the transition cow. Significant increases in plasma nonesterified fatty acids contribute to oxidative stress and uncontrolled inflammatory responses. A dysfunctional inflammatory response is the common link between metabolic and infectious diseases around the time of calving. Intervention strategies that can reduce lipid mobilization may improve inflammatory responses and reduce the economic losses associated with health disorders during the transition period., (Copyright © 2013 Elsevier Inc. All rights reserved.)

These case reports demonstrated the diagnostic dilemma encountered in patients with systemic lupus erythematosus and thrombotic thrombocytopenic purpura particularly in settings with limited diagnostic facilities and laboratory support. The similarities in the diagnostic criteria for both conditions make clear distinction as well as management decisions difficult. We present the difficulties encountered with both the diagnosis and the management of these two patients that were managed in our facility., (Copyright © 2013 Wiley Periodicals, Inc.)

We present a case of a woman with a 14-year history of rheumatoid arthritis, who showed simultaneously and gradually appearing, annular, erythematous, itchy patches and exacerbation of the joint symptoms, of one month duration, after pregnancy. Clinical and histologic features led us to the diagnosis of erythema multiforme. While it is not possible to exclude that the co-occurrence of the two conditions is coincidental, our case suggests the possibility that erythema multiforme is a sign of an ample alteration of the immune system that may occur in patients with systemic immune diseases as a consequence of the action of various triggering factors, such as molecular mimicry between endogenous and exogenous antigens or pregnancy, which is notoriously a period of complex and still largely unexplored alterations in the immune system reactivity.

A case of 26 year-old female with peripartum cardiomyopathy, acute pancreatitis, periadipose tissue inflammation due to unknown cause and multiple organ dysfunction syndrome complication is presented.

Whereas neutrophils are the main phagocytic leukocytes, monocytes and macrophages are actively involved in immunomodulation after infection. Recent studies have demonstrated that neutrophil function is impaired by the state of negative energy balance around parturition, and that cows that develop uterine disease have a greater degree of negative energy balance than healthy cows. The objectives of this study were to compare monocyte gene expression and protein secretion of selected cytokines from calving to 42 d after calving in Holstein cows that did or did not develop uterine disease. Real time quantitative RT-PCR (Tumor necrosis factor-α (TNFα), Interleukin (IL)-1β, IL-6, IL-8 and IL-10) and ELISA (TNFα, IL-1β and IL-8) were used to evaluate cytokine response following in vitro stimulation of blood-derived monocytes with irradiated E. coli. Relative to unstimulated cells, E. coli-stimulated monocytes from cows with metritis had lower gene expression of key pro-inflammatory cytokines than healthy cows from calving to 14 d after calving (TNFα at 0, 7, and 14 d after calving, IL-1β and IL-6 at 7 and 14 d after calving; P < 0.05). There were no significant differences between groups for expression of IL-8 or the anti-inflammatory cytokine IL-10. This was due, in part, to higher gene expression in unstimulated monocytes (TNFα, IL-1β, IL-6 and IL-10) in early lactation from cows with metritis. Expression of mRNA in stimulated cells (relative to housekeeping genes) was lower for TNFα (7 and 14 d postpartum) and for IL-10 (7 and 14 d postpartum) in cows with metritis. Concentration of TNFα was lower in the culture medium of E. coli-stimulated monocytes from cows with metritis than healthy cows at calving and 7 and 21 d after calving (P < 0.05). Circulating cytokine concentrations were not different between groups for IL-8 and were below the limits of detection for TNFα and IL-1β. Cytokine gene expression and production were similar between healthy cows and cows that developed endometritis, diagnosed cytologically at 42 d after calving. We concluded that altered levels of expression and production of pro-inflammatory cytokines postpartum could contribute to impaired inflammatory response and predispose cows to development of metritis., (Copyright © 2012 Elsevier Inc. All rights reserved.)

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.

The aim of the present study was to analyse the effect of subclinical endometritis on endometrial and embryonic gene expression. A total of 49 cows at either Day 0 or Day 7 of the oestrous cycle (62-83 days post partum) following superovulation were classified as having subclinical endometritis (SE-0, SE-7) or a healthy endometrium (HE-0, HE-7) on the basis of endometrial cytological evaluation. Endometrial samples and associated embryos were subjected to global transcriptome analysis using the Bovine GeneChip (Affymetrix, Santa Clara, CA, USA) and aberrant transcript profiles were observed in SE-0 and SE-7 cows. At Day 0, 10 transcripts were found to be differentially expressed in endometrial samples. Specifically, the PDZK1, PXDN, DDHD2, GPLD1 and SULT1B1 genes were downregulated, whereas the PKIB, LOC534256, BT29392, LYZ and S100A14 genes were upregulated in SE-0 cows. Similarly, 11 transcripts were found to be differentially regulated on Day 7. Of these, GNPTG, BOLA-DQA5, CHD2, LOC541226, VCAM1 and ARHGEF2 were found to be downregulated, whereas PSTPIP2, BT236441 and MGC166084 were upregulated in SE-7 cows. Accordingly, endometrial health status affected the number of flushed, transferable embryos. In all, 20 genes were differentially regulated in blastocysts derived from HE-7 and SE-7 cows. Of these, GZMK, TCEAL4, MYL7, ADD3 and THEM50B were upregulated, whereas NUDCD2, MYO1E, BZW1, EHD4 and GZMB were downregulated. In conclusion, endometrial polymorphonuclear neutrophil infiltration as an indicator of subclinical endometritis is associated with changes in endometrial gene expression patterns, including genes involved in cell adhesion and immune modulation. Consequently, subclinical endometritis affects gene expression in embryos, including the expression of genes related to membrane stability, the cell cycle and apoptosis.

This paper briefly reviews recent data and concepts on the development and mitigation of infection and inflammation in the reproductive tract of dairy cows during the first 2 mo after calving. The incidence of metritis is typically between 10 and 20%, of clinical endometritis or purulent vaginal discharge (PVD) approximately 15%, and of subclinical or cytological endometritis a further 15%. Worse postpartum negative energy balance is associated with more severe or prolonged uterine inflammation. Changes in feed intake, expression of genes for pro-inflammatory cytokines, notably interleukin (IL) 1, IL6 and IL8, circulating concentrations of beta-hydroxybutyrate (BHBA) or nonesterified fatty acids (NEFA), and innate immune function precede both metritis and endometritis by several weeks. Infections with Escherichia coli and Arcanobacterium pyogenes are associated with both metritis and PVD. There are new data to suggest that specific virulence factors in E. coli associated with adherence may be important in metritis and PVD. Cytological endometritis and PVD are overlapping but largely distinct conditions, and there are emerging data that cervicitis exists both concurrent with and separate from endometritis. Much remains to be learned about what initiates and sustains harmful inflammation of the reproductive tract. Such information is necessary to develop effective treatments for the various forms of disease and, more importantly, to develop means to prevent endometritis and cervicitis. In particular, vaccination against specific uterine pathogens and interventions to modulate innate immune response appear to be important avenues for investigation. Presently, commonly recommended best management practices for cows in the transition period are likely to be helpful to mitigate the risk of reproductive disease., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: Postpartum thyroid dysfunction (PPTD) occurs in the first 12 months after delivery. This work was designed to compare thyroid peroxidase (TPO) and thyroglobulin (Tg) autoantibodies for determination of the diagnosis and, also, to detect role of lymphocytes in the pathogenesis of autoimmune thyroiditis., Methods: This study was conducted on 50 females in postpartum period. Thyroid hormones, TPO- and Tg-Abs, and percentages of blood lymphocytes were determined., Results: The TPO-Abs were positive in 1(4%),10 (66.7%),6 (60%) of the control, hyperfunction, and hypofunction groups, respectively. The Tg-Abs were positive in 1(4%), 8 (533%), 5 (50%) of same groups, respectively. There was significant negative correlation between serum FT4 and TPO and Tg antibody titers in the hypofunction group. In cases with positive TPO-Abs, there were significantly decreased natural killer cells (NK) and significantly increased activated T cells when compared to the control group and to the TPO negative cases., Conclusions: The TPO Ab was more sensitive than Tg Ab in predicting PPTD and a high titer of both correlates with the severity of hypothyroidism. Two forms of PPTD appeared to exist: autoimmune form characterized by positive TPO-Ab and increased activated T cells and reduced NK cells and a non immune form without these characteristics.

Introduction: The Oxford Programme for Immunomodulatory Immunoglobulin Therapy has been operating since 1992 at Oxford Radcliffe Hospitals in the UK. Initially, this program was set up for patients with multifocal motor neuropathy or chronic inflammatory demyelinating poly-neuropathy to receive reduced doses of intravenous immunoglobulin (IVIG) in clinic on a regular basis (usually every 3 weeks). The program then rapidly expanded to include self-infusion at home, which monitoring showed to be safe and effective. It has been since extended to the treatment of other autoimmune diseases in which IVIG has been shown to be efficacious., Methods: This review includes details of the program such as the training of patients, dosing with immunoglobulin, and monitoring and compliance for self-infusion at home, with cases to illustrate these points., Results: In addition, the Evidence for efficacy and the effects of confounding morbidities will be are included described. More recently, subcutaneous immunoglobulin therapy (SCIG) has been used in several chronic autoimmune peripheral neuropathies and in epidermolysis bullosa acquisita, with equally good effect. Trials of SCIG in other autoimmune diseases are planned.

Objectives: To determine whether changes in levels of anti-cyclic citrullinated peptide (anti-CCP) and rheumatoid factor (RF) are associated with the spontaneous improvement of rheumatoid arthritis (RA) during pregnancy and with the subsequent flare post partum., Methods: Disease activity scores from the Pregnancy-induced Amelioration of Rheumatoid Arthritis (PARA) study of 118 patients were available for analysis. Before conception (if applicable), at each trimester and at 6, 12 and 26 weeks post partum, levels of the autoantibodies anti-CCP, IgM-RF, IgG-RF and IgA-RF were determined. Responses in disease activity were classified according to European League Against Rheumatism (EULAR) response criteria during pregnancy and post partum, and associated with the presence or absence of autoantibodies., Results: The median levels of anti-CCP and all subclasses of RF during pregnancy were stable, whereas post partum the levels of anti-CCP, IgM-RF and IgA-RF declined. A significantly higher percentage of women without autoantibodies (negative for anti-CCP and RF) improved compared with women positive for either or both autoantibodies (75% vs 39%, p = 0.01). The occurrence of a flare post partum was comparable between these groups., Conclusions: Improvement of disease activity of RA during pregnancy was not associated with changes in levels of autoantibodies during pregnancy, however, improvement may occur more frequently in the absence of anti-CCP and RF.

Objectives: To investigate the influence of pregnancy and postpartum on rheumatoid arthritis (RA) course and the impact of maternofetal HLA class II disparity., Methods: In 13 women with RA, disease activity was assessed prospectively, before and every three months throughout pregnancy and after delivery until one year in postpartum. The HLA class II disparity was evaluated by typing HLA-DRB1, DQB1 and DQA1 alleles by the PCR-SSOP for 12 couples mothers and babies. Furthermore, for three women, RA disease activity during a previous pregnancy was evaluated retrospectively and HLA typing was performed for the three children., Results: The mean age of patients was 30+/-5 years. All women had successful pregnancy. During pregnancy, a favourable RA outcome was noted in 62.5% of cases. Three patients were in remission after conception. Persistent disease activity was noted in 30% of cases. In postpartum, disease relapse occurred in 92% of cases at a mean delay of 80+/-63 days. Three women did not resume the initial modifying antirheumatic drugs (DMARDs) 12 months after delivery. For others, the mean delay was 6+/-3.5 months. There was no significant correlation between the clinicoradiological parameters and the RA outcome. We noted a tendency towards correlation between male newborns and an unfavourable RA outcome (p=0.059). A high degree of maternofetal disparity in HLA class II was seen in 73.5% of cases. We observed a more marked improvement in disease activity parameters in case of more than one disparity but without a significant statistical difference., Conclusion: A favourable RA outcome during pregnancy in about two-thirds of the cases and a frequent relapse after delivery were observed. RA activity improvement is more obvious at the end of pregnancy. A high degree of maternofetal HLA class II disparity seems to modulate RA disease activity., (Copyright 2009 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

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.

Postpartum-acquired haemophilia A is a rare but potentially severe complication of pregnancy. Although the natural history of the disease is usually benign, with a high percentage of spontaneous remissions and a low mortality, its quick recognition is important to control bleeding episodes. The therapeutic strategies in these patients are the treatment of acute bleeding episodes and the long-term eradication of the autoantibody. We report three different cases of postpartum-acquired haemophilia demonstrating the broad heterogeneity of the clinical presentation and of therapeutic necessity of this condition. Finally, we present a review of the literature on the current therapeutic management of this haemorrhagic disorder.

Bovine uterine disease reduces milk yield, impairs fertility and has implications for animal welfare. During involution, the uterus is usually exposed to multiple potential bacterial pathogens which are cleared by successful orchestration of the local inflammatory response. Unsuccessful resolution leads to the development of disease. The aim of this study was to characterize the local innate immune response in the uterus during physiological involution using histopathological and molecular analyses in 9 cows, 2 weeks after calving (early postpartum, EPP), and 4 cows, 9 weeks after calving (late postpartum, LPP). Uterine biopsies taken from each cow were classified by histopathology, and RNA was extracted for molecular analysis. Two EPP cows were classified with a mild, 5 with a moderate and 2 with a severe inflammatory response. Relative gene expression analysis was then performed using quantitative real-time PCR (qRT-PCR) and specific primers for genes encoding Toll-like receptors (TLRs), chemokines, cytokines, acute phase proteins (APPs) and antimicrobial peptides (AMPs). TLR4, transcription factor NFKB1 and the inflammatory cytokines IFNG, IL1A, IL6, IL8, IL12A were all significantly increased in EPP cows (P<0.05). Increase in HP, SAA3, TAP and DEFB5 genes was particularly marked in cows with severe inflammation. These results reveal evidence of an inflammatory uterine environment in the early postpartum period with significant induction of both AMP and APP genes. Histopathological grades in EPP cows are underpinned by quantitative changes in gene expression. Understanding the molecular mechanisms contributing to uterine immunity in the early postpartum period may identify candidate genes associated with the resolution of inflammation.

Dairy cattle are susceptible to increased incidence and severity of disease during the periparturient period. Increased health disorders have been associated with alterations in bovine immune mechanisms. Many different aspects of the bovine immune system change during the periparturient period, but uncontrolled inflammation is a dominant factor in several economically important disorders such as metritis and mastitis. In human medicine, the metabolic syndrome is known to trigger several key events that can initiate and promote uncontrolled systemic inflammation. Altered lipid metabolism, increased circulating concentrations of non-esterified fatty acids and oxidative stress are significant contributing factors to systemic inflammation and the development of inflammatory-based diseases in humans. Dairy cows undergo similar metabolic adaptations during the onset of lactation, and it was postulated that some of these physiological events may negatively impact the magnitude and duration of inflammation. This review will discuss how certain types of fatty acids may promote uncontrolled inflammation either directly or through metabolism into potent lipid mediators. The relationship of increased lipid metabolism and oxidative stress to inflammatory dysfunction will be reviewed as well. Understanding more about the underlying cause of periparturient health disorders may facilitate the design of nutritional regimens that will meet the energy requirements of cows during early lactation and reduce the susceptibility to disease as a function of compromised inflammatory responses.

Objective: We examined the association between biochemical parameters of stress in puerperae and immune substances in breast milk., Methods: The participants were 22 mothers 2 weeks after delivery, with normal pregnancy/delivery and a normal puerperal course. We measured the levels of secretory immunoglobulin A (SIgA) and cortisol in saliva and the level of SIgA and the leukocyte count in breast milk and investigated their association., Results: There was a positive correlation between the salivary and breast milk levels of SIgA (r = .536, p < .05). However, there were no correlations among the salivary level of cortisol and the level of SIgA and leukocyte count in breast milk., Conclusions: The only association found in our study was between the salivary and breast milk SIgA. The lack of association among SIgA and cortisol may be related to a variety of factors such as production site, diurnal rhythms, and the interval between stress stimulation in mothers and the response of the biomarker.

We describe the case of a 30-year-old woman who, 5 days after giving birth to her first child by cesarean section, presented with dehiscence of one end of the surgical wound and a lesion on her leg that developed into a well-defined ulcer; both lesions were very painful. The patient was initially diagnosed with a skin infection and later with superficial pyoderma gangrenosum. The lesions were treated with topical corticosteroids and a good response was observed. No evidence was found of underlying disease. Isolated cases of pyoderma gangrenosum associated with pregnancy or cesarean delivery have been reported in the literature. The etiology of pyoderma gangrenosum is currently unknown, but some theories suggest an immunologic mechanism. Gestation is known to generate a state of immune tolerance that could play a role in the development of the disease and future studies may help to clarify the significance of this association.

A number of antioxidants and trace minerals have important roles in immune function and may affect health in transition dairy cows. Vitamin E and beta-carotene are important cellular antioxidants. Selenium (Se) is involved in the antioxidant system via its role in the enzyme glutathione peroxidase. Inadequate dietary vitamin E or Se decreases neutrophil function during the perpariturient period. Supplementation of vitamin E and/or Se has reduced the incidence of mastitis and retained placenta, and reduced duration of clinical symptoms of mastitis in some experiments. Research has indicated that beta-carotene supplementation may enhance immunity and reduce the incidence of retained placenta and metritis in dairy cows. Marginal copper deficiency resulted in reduced neutrophil killing and decreased interferon production by mononuclear cells. Copper supplementation of a diet marginal in copper reduced the peak clinical response during experimental Escherichia coli mastitis. Limited research indicated that chromium supplementation during the transition period may increase immunity and reduce the incidence of retained placenta.

The post-partum period in cattle is characterised by an increased risk of infection of the uterus, as the anatomical barriers are broached during parturition and remain open for several days. Infection of the uterus is largely influenced by the balance between bacterial contamination and the local and systemic immune status during pregnancy and around parturition. Infectious diseases are more prevalent during this period, because of an impaired immune status before and immediately after parturition. Neutrophils play a primary role in the defence of the uterus against infection. Influx of neutrophils into the uterus is thought to be mediated by chemoattractants, chemokines and adhesion molecules, such as beta2-integrin (complement receptor 3) and L-selectin (CD62L). Other cellular components activated in the uterus during this period include lymphocytes, eosinophils, mast cells and macrophages. The major classes of immunoglobulins (IgM, IgA and IgG), either by passive diffusion or local production, play an important protective role in the uterus by acting as opsonins to enhance phagocytosis, stimulating the complement pathways or blocking pathogens from adhering to mucosal surfaces. Endometrial cells express toll-like receptor 4 (TLR4), which recognises lipopolysaccharides of Escherichia coli and other Gram negative bacteria, the most common causes of bovine endometritis. Activation of TLR4 triggers the production of tumour necrosis factor alpha and other pro-inflammatory cytokines. The periparturient period is also characterised by an increased secretion of prostaglandin F(2alpha), which enhances uterine immune defences.

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.