Prevalence of Coeliac Disease in Omani Adults with Iron Deficiency Anaemia of Unknown Cause: Case-finding study.

Objectives: This study aimed to estimate the serological prevalence of coeliac disease in patients with iron deficiency anaemia (IDA) of unknown cause at a primary healthcare facility in Oman. Methods: This prospective case-finding study was conducted at the primary care clinics in Sultan Qaboos University Hospital, Muscat, Oman from September 2018 to June 2020. Patients aged 18 to 55 years, with a haemoglobin (Hb) level <11.5 g/dL for males and <11.0 g/dL for females and a ferritin level <30 ng/mL for males and <13 ng/mL for females, were included in the study. Blood samples were obtained for initial serological screening using serum immunoglobulin (Ig)A level; those samples with normal levels of IgA, IgA anti-tissue transglutaminase antibody (tTG) and IgA anti-deamidated gliadin peptide (DGP) were determined. Positive IgA-tTG test was confirmed using IgA-endomysial antibodies. Patients with low IgA levels were tested using IgG-tTG and IgG-DGP. Results: A total of 104 patients participated in this study. Eight patients (7.7%) were found to have a positive serological screening result for coeliac disease; of these patients, three (37.5%) had a positive IgA-tTG result. Two of those three (66.7%) had a positive IgA-endomysial antibody. The IgA-DGP result was positive in seven (6.7%) of the 104 patients. Out of those seven patients, two also had a positive IgA tTG. Conclusion: Coeliac disease is not a rare disorder. There is a need to increase awareness among healthcare professionals about coeliac disease and its non-classical manifestations such as IDA.

Malformin-A1 (MA1) Sensitizes Chemoresistant Ovarian Cancer Cells to Cisplatin-Induced Apoptosis.

High-grade epithelial ovarian cancer is a fatal disease in women frequently associated with drug resistance and poor outcomes. We previously demonstrated that a marine-derived compound MalforminA1 (MA1) was cytotoxic for the breast cancer cell line MCF-7. In this study, we aimed to examine the effect of MA1 on human ovarian cancer cells. The potential cytotoxicity of MA1was tested on cisplatin-sensitive (A2780S) and cisplatin-resistant (A2780CP) ovarian cancer cell lines using AlamarBlue assay, Hoechst dye, flow cytometry, Western blot, and RT-qPCR. MA1 had higher cytotoxic activity on A2780S (IC50 = 0.23 µM) and A2780CP (IC50 = 0.34 µM) cell lines when compared to cisplatin (IC50 = 31.4 µM and 76.9 µM, respectively). Flow cytometry analysis confirmed the cytotoxic effect of MA1. The synergistic effect of the two drugs was obvious, since only 13% of A2780S and 7% of A2780CP cells remained alive after 24 h of treatment with both MA1 and cisplatin. Moreover, we examined the expression of bcl2, p53, caspase3/9 genes at RNA and protein levels using RT-qPCR and Western blot, respectively, to figure out the cell death mechanism induced by MA1. A significant down-regulation in bcl2 and p53 genes was observed in treated cells compared to non-treated cells (p < 0.05), suggesting that MA1 may not follow the canonical pathway to induce apoptosis in ovarian cancer cell lines. MalforminA1 showed promising anticancer activity by inducing cytotoxicity in cisplatin-sensitive and cisplatin-resistant cancer cell lines. Interestingly, a synergistic effect was observed when MA1 was combined with cisplatin, leading to it overcoming its resistance to cisplatin.

Overlapping demyelinating syndrome (Neuromyelitis optica spectrum disorders NMOSD with anti-NMDA receptor encephalitis); A case report.

Neuromyelitis optica spectrum disorder (NMOSD) represents an evolving spectrum of inflammatory demyelinating central nervous system-based autoimmune diseases; while anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is another severe immune-mediated syndrome that occurs in association with IgG antibodies against the GluN1 subunit of the NMDAR and has been predominantly reported in young females (Dalmau et al., 2008 Dec). Although It has been recognized that anti-NMDAR encephalitis can coexist in the same patient who has serological markers of another autoimmune disease (e.g. neuronal autoantibodies and demyelination AQP4 or MOG antibodies) (Titulaer et al., 2014), rare cases are reported with anti-NMDAR encephalitis that overlap with a demyelinating syndrome; such as neuromyelitis optica spectrum disorders associated with Anti- Aquaporin 4 (AQP4) antibodies (Titulaer et al., 2013). We report here an unusual and rare overlapping autoimmune syndrome in a young Omani female who first presented in 2011 with the clinical and radiological presentations of neuromyelitis optica spectrum disorder (NMOSD) and had a complete recovery. Five years later, she was admitted with the diagnosis of anti-NMDAR encephalitis and was found to have positive serum as well as CSF analyses results for AQP4 and anti-NMDAR antibodies. The patient showed significant improvement, for both clinical syndromes with good response to steroid and immunomodulating therapy.

A Decade Experience on Severe Combined Immunodeficiency Phenotype in Oman, Bridging to Newborn Screening.

Introduction: Severe combined immunodeficiency (SCID) results from various monogenic defects that impair immune function and brings on early severe and life-threatening infections. The main stay of treatment for SCID is hematopoietic stem cell transplant (HSCT) with near normal survival at 5 years for an early transplant done at or before the age of 3.5 months of life and the patient is maintained free of infections. Although overall rare, it constitutes a major burden on affected children, their families and on the health system especially in communities with a high rate of consanguinity where incidence and prevalence of recessive inborn errors of immunity (IEI) are expected to be high. Method: Here, we report the clinical, immunological, and molecular findings in 36 children diagnosed with SCID from a single tertiary center in Oman for the last decade. Results: We observed a median annual incidence rate of 4.5 per 100,000 Omani live births, and 91.7% of affected children were born to consanguineous parents. Twenty-three children (63.9%) fulfilled the criteria for typical SCID. The median age at onset, diagnosis and diagnostic delay were 54, 135, and 68 days, respectively. The most common clinical manifestations were pneumonia, septicemia, and chronic diarrhea. Eleven children (30.6%) have received hematopoietic stem cell transplant (HSCT) with a survival rate of 73%. The most frequent genetic cause of SCID in this cohort (n = 36) was (RAG-1), encoding for recombination activating gene (n = 5, 13.9%). Similarly, Major histocompatibility complex type II deficiency accounted for (n = 5, 13.9%) of our cohort. Conclusion: Our report broadens the knowledge of clinical and molecular manifestations in children with SCID in the region and highlights the need to initiate newborn based screening program (NBS) program.

STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles.

A subset of human follicular helper T cells (TFH) cells expresses CD57 for which no distinct function has been identified. We show that CD57+ TFH cells are universally PD-1hi, but compared to their CD57- PD-1hi counterparts, express little IL-21 or IL-10 among others. Instead, CD57 expression on TFH cells marks cytotoxicity transcriptional signatures that translate into only a weak cytotoxic phenotype. Similarly, circulating PD-1+ CD57+ CD4+ T cells make less cytokine than their CD57- PD-1+ counterparts, but have a prominent cytotoxic phenotype. By analysis of responses to STAT3-dependent cytokines and cells from patients with gain- or loss-of-function STAT3 mutations, we show that CD4+ T cell cytotoxicity is STAT3-dependent. TFH formation also requires STAT3, but paradoxically, once formed, PD-1hi cells become unresponsive to STAT3. These findings suggest that changes in blood and germinal center cytotoxicity might be affected by changes in STAT3 signaling, or modulation of PD-1 by therapy.

Heterophile interference accounts for method-specific dsDNA antibodies in patients receiving anti-TNF treatment.

OBJECTIVE: To evaluate analytical explanations for the highly reported incidence of antibodies to dsDNA in patients receiving TNF antagonists. METHODS: Sixty serum samples from patients receiving biological anti-TNF medication were assessed for the presence of dsDNA antibodies using three standard diagnostic platforms [ELISA, IIF and multiplex bead array (MBA)], before and after treatment to block heterophile antibodies. Results were compared with those obtained using serum samples from patients with SLE. RESULTS: We identified significant method-specific discrepancies in the estimation of dsDNA antibodies in patients receiving TNF antagonists. dsDNA antibodies were frequent according to ELISA and IIF, but rare according to MBA. Blockade of heterophile antibodies resulted in a significant reduction in titres of dsDNA antibodies detected by IIF. In contrast, there was a much greater consistency for dsDNA antibody results in SLE, especially for those present in high titre, and blockade of heterophile antibodies did not result in a change between the two paired samples by IIF or MBA. CONCLUSION: There is a significant method-specific variation in the detection of dsDNA antibodies in patients receiving TNF antagonists, due in part to the effects of heterophile antibodies.