A 15-year-old boy was admitted to the emergency department with arthralgia of the knee. He was diagnosed with acute rheumatic fever based on clinical examination, electrocardiography, echocardiography, and elevated inflammatory markers including C-reactive protein, erythrocyte sedimentation rate, and anti-streptolysin O titre. First-degree and second-degree Mobitz type 1 atrioventricular blocks, moderate frequency uniform ventricular premature beats, as well as non-sustained ventricular tachycardia, were detected on 24-hour Holter electrocardiography monitoring.

Foetomaternal microchimerism establishes a lifelong reciprocal exchange of immune cells that shapes immunity in both mother and offspring. Foetal microchimeric cells (FMc) include CD34+ progenitors, CD8+ CTLs and Th2-polarized lymphocytes that integrate into maternal bone marrow, spleen and inflamed tissues, promoting peripheral tolerance via Treg (FOXP3+CD4+) expansion, CTLA-4 upregulation and IL-10/TGF-β secretion, while inhibiting CD8+ cytotoxicity through clonal deletion and CXCR3 downregulation. Conversely, maternal microchimerism (MMc) transfers memory T cells, CD34+ HSCs and innate effectors (macrophages, NK cells) to the foetal thymus and lymphoid tissues, driving NIMA-specific Treg differentiation via CNS1-dependent Foxp3 induction and PD-L1+ DC suppression of Th1/Th17 responses. HLA class II incompatibility, complement (C3/C5a) and CCL2/CCR2 signalling coordinate this cellular crosstalk. Clinically, FMc enhances maternal tissue repair and cancer surveillance but increases autoimmune risk in scleroderma and PBC; MMc boosts newborn pathogen resistance and reduces GVHD in NIMA-matched HSCT. This review establishes microchimerism as a crucial regulator of intergenerational immunological homeostasis.

In this study, we examined the yield of routine cerebrospinal fluid (CSF) analysis to assess for an autoimmune etiology in patients with chronic seizures of unknown cause. Forty-seven patients were included. Six of 47 (13%) had inflammation on routine CSF analysis, none of whom were diagnosed with seizures related to autoimmune encephalitis (AE). Meanwhile, 2/47 (4%) were diagnosed with seizures related to AE, neither of whom had inflammation on routine CSF analysis. Routine CSF analysis to assess for an autoimmune etiology in patients with chronic seizures of unknown cause is low yield, and has suboptimal specificity and sensitivity for seizures related to AE.

High anti-GAD65 levels associate with core manifestations of GAD65 neurological autoimmunity. ELISA cut-offs for high anti-GAD65 levels (>10,000 IU/ml in serum, >100 IU/ml in CSF) have been proposed that merit further evaluation. We reviewed patients who underwent anti-GAD65 ELISA for suspected autoimmune encephalitis and found values above these cut-offs to have a positive predictive value (PPV) for neurological autoimmunity of 88%. Anti-GAD65 values above proposed ELISA cut-offs have a reasonably high PPV for neurological autoimmunity in patients with suspected autoimmune encephalitis. Consideration of alternative diagnoses and corroboration with CSF can help flag potentially clinically irrelevant results and avoid patient misdiagnosis.

The objective of this study was to determine the association between birthweight and risk of thyroid and autoimmune conditions in a large sample of postmenopausal women. Baseline data from the Women’s Health Initiative (n = 80,806) were used to examine the associations between birthweight category (<6 lbs., 6–7 lbs. 15 oz, 8–9 lbs. 15 oz, and ≥10 lbs.) and prevalent thyroid (underactive and overactive thyroid and goiter) and autoimmune (lupus, rheumatoid arthritis (RA), multiple sclerosis, ulcerative colitis/Crohn’s disease) conditions. Follow-up questionnaire data were used to examine the associations between birthweight and incident underactive and overactive thyroid, lupus, and RA. Logistic and Cox proportional hazards regression models were used to estimate crude and adjusted odds (OR) and hazards ratios (HR), respectively. Overall, women born weighing ≥10 lbs. had an increased risk for underactive thyroid [OR 1.14 (95% CI 1.02, 1.28)] and incident lupus [HR 1.51 (95% CI 1.12, 2.03)] and a decreased risk for overactive thyroid [OR 0.67 (95% CI 0.50, 0.92)] compared to women born weighing 6–7.99 lbs., after adjustment for adult BMI, demographic variables, and lifestyle factors. Further, women born weighing <6 lbs. were at increased risk for underactive thyroid [OR 1.13 (95% CI 1.04, 1.22)]. Birthweight was not associated with other thyroid or autoimmune disorders. High birthweight was associated with later-life thyroid and autoimmune conditions while low birthweight was associated with underactive thyroid. Preconception and prenatal interventions aimed at reducing the risk of both high and low birthweights may reduce the burden of later-life thyroid and autoimmune conditions.

The term ‘epigenetics’ refers to a series of meiotically/mitotically inheritable alterations in gene expression, related to environmental factors, without disruption on DNA sequences of bases. Recently, the pathophysiology of autoimmune diseases (ADs) has been closely linked to epigenetic modifications. In fact, epigenetic mechanisms can modulate gene expression or repression of targeted cells and tissues involved in autoimmune/inflammatory conditions acting as keys effectors in regulation of adaptive and innate responses. ADs, as systemic lupus erythematosus (SLE), a rare disease that still lacks effective treatment, is characterised by epigenetic marks in affected cells. Taking into account that epigenetic mechanisms have been proposed as a winning strategy in the search of new, more specific and personalised therapeutics agents, pharmacology and pharmaco-epigenetic studies about epigenetic regulations of ADs may provide novel individualised therapies. Focusing on possible implicated factors on development and predisposition of SLE, diet is feasibly one of the most important factors since it is linked directly to epigenetic alterations and these epigenetic changes may augment or diminish the risk of SLE. Nevertheless, several studies have suggested that dietary therapy could be promising to SLE patients via prophylactic actions deprived of side effects of pharmacology, decreasing co-morbidities and improving lifestyle of SLE sufferers. Herein, we review and discuss the cross-link between epigenetic mechanisms on SLE predisposition and development, as well as the influence of dietary factors on regulation of epigenetic modifications that may eventually make a positive impact on SLE patients.

Hemophagocytic lymphohistiocytosis (HLH) is a rare immune deregulatory disorder that predominantly presents in children. Here we describe three patients with adult-onset primary HLH whose initial presentations were characterized by neurological features, and we review the literature of published cases. These cases ranged in age from 17 to 30 and presented with a variety of neurological symptoms. One of our cases demonstrated numerous microhemorrhages on MR brain. This is the first published case of adult-onset HLH presenting with cerebral microhemorrhages. In addition, literature review identified five additional patients with isolated central nervous system presentation of primary HLH.