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To address inborn errors of immunity (IEI) which were underdiagnosed in resource-limited regions, our centre developed and offered free genetic testing for the most common IEI by Sanger sequencing (SS) since 2001. With the establishment of The Asian Primary Immunodeficiency (APID) Network in 2009, the awareness and definitive diagnosis of IEI were further improved with collaboration among centres caring for IEI patients from East and Southeast Asia. We also started to use whole exome sequencing (WES) for undiagnosed cases and further extended our collaboration with centres from South Asia and Africa. With the increased use of Next Generation Sequencing (NGS), we have shifted our diagnostic practice from SS to WES. However, SS was still one of the key diagnostic tools for IEI for the past two decades. Our centre has performed 2,024 IEI SS genetic tests, with in-house protocol designed specifically for 84 genes, in 1,376 patients with 744 identified to have disease-causing mutations (54.1%). The high diagnostic rate after just one round of targeted gene SS for each of the 5 common IEI (X-linked agammaglobulinemia (XLA) 77.4%, Wiskott–Aldrich syndrome (WAS) 69.2%, X-linked chronic granulomatous disease (XCGD) 59.5%, X-linked severe combined immunodeficiency (XSCID) 51.1%, and X-linked hyper-IgM syndrome (HIGM1) 58.1%) demonstrated targeted gene SS should remain the first-tier genetic test for the 5 common X-linked IEI.

Purpose: This study aims to report correlations between thyroid-stimulating immunoglobulin (TSI) and both clinical and radiological parameters in recent-onset symptomatic thyroid eye disease (TED) patients. Methods: A prospective cohort study of TED patients managed at the Chinese University of Hong Kong from January 2014 to May 2022. Serum TSI levels were determined with the functional assay. Outcomes included the Clinical Activity Score (CAS), marginal reflex distance1 (MRD1), extraocular muscle motility restriction (EOMy), exophthalmos, and diplopia. The radiological assessment included cross-sectional areas and signal of extraocular muscles on STIR-sequence MRI. Results: A total of 255 (197 female) treatment-naive patients, with an average onset age of 50 ± 14 years (mean ± s.d.), were included. Elevated pre-treatment TSI level was observed in 223 (88%) patients. There was a weak positive correlation between TSI and CAS (r = 0.28, P = 0.000031), MRD1 (r = 0.17, P = 0.0080), and the size of the levator palpebrae superioris/superior rectus complex (r = 0.25, P = 0.018). No significant correlation existed between TSI and STIR signals. The AUC and optimal cut-off value for clinical active TED were 0.67 (95% CI: 0.60–0.75) and 284% (specificity: 50%, sensitivity: 85%). In total, 64 patients received intravenous methylprednisolone (IVMP) during the study interval, and they had a higher baseline TSI level than those who did not have IVMP (P = 0.000044). Serial post-IVMP TSI among the 62 patients showed a significant reduction compared to the baseline level (P < 0.001). Both the baseline and post-IVMP TSI levels, and percentages of TSI changes were comparable between patients who responded and did not respond to the first course of IVMP. Conclusion: TSI can be a serum biomarker for the diagnosis, prognosis, and treatment response of TED. Further validation should be warranted.

BackgroundAdult antibody deficiency remains under-recognised and under-studied – especially among Asian populations. Patterns of immunoglobulin use and the feasibility of subcutaneous immunoglobulin (SCIg) replacement among Chinese patients remains unclear.ObjectiveTo investigate the trends of immunoglobulin use, burden of adult antibody deficiency and the outcomes of patients on SCIg compared to intravenous immunoglobulin (IVIg) replacement in Hong Kong through a retrospective observational study.MethodsPopulation-wide data of immunoglobulin recipients in Hong Kong between 2012 and 2021, and longitudinal clinical data of adult immunodeficiency patients at Queen Mary Hospital were collected and analysed.ResultsTotal immunoglobulin consumption and recurrent immunoglobulin recipients increased continuously from 175,512g to 298,514g (ρ=0.99, p

The availability of next-generation sequencing (NGS) helps to resolve many of the diagnostic odysseys. Common variable immunodeficiency disease (CVID) is an entity encompassing a heterogenous group of conditions with hypogammaglobulinemia, and it is a diagnosis of exclusion. In recent years, with the advances of molecular diagnostics, more and more patients have been reclassified with more defined entities after their genetic causes were found. Here, we reported a young man, who was managed as CVID since childhood, presenting with recurrent infection, hypogammaglobulinemia, and immune thrombocytopenia (ITP). Finally, more than a decade after initial presentation, gene panel testing revealed a novel mutation in the MAGT1 gene. Collectively, the genetic findings and clinical presentations confirm the diagnosis of X-linked immunodeficiency with magnesium defect and Epstein–Barr virus infection and neoplasia (XMEN). MAGT1 is an evolutionarily conserved, magnesium-specific transporter expressed in all mammalian cells that plays an essential role in magnesium homeostasis. MAGT1 also acts as an accessory protein for STT3B, as catalytic subunits of the oligosaccharyltransferase protein complex, which carries out glycan chain transfer to proteins in the endoplasmic reticulum during N-glycosylation. Glycans play an essential role in the stability, maturation, and localization in glycoproteins that are important in our immune cells’ function. Mutation of the gene resulted in a rare X-linked recessive condition XMEN. The disease has complete penetrance but variable expressivity. It is mainly associated with immunodeficiency, immunodysregulation, and predisposition to EBV-associated lymphoproliferation. Extraimmune manifestations have also been reported in some patient cohorts, including hepatic and neurological abnormalities. Overall, the presentation varies among patients and overlaps with other clinical entities, in which diagnosis is challenging. Before the era of NGS, traditional workup hinges heavily on phenotype studies, followed by single-gene sequencing. The diagnostic yield is low, and a significant delay in diagnosis is common. This case illustrated the importance of early consideration of molecular studies in complex immunological cases without obvious secondary causes as an integral part of patient management.

Abstract Aims To investigate any seasonality in the incidence of anti‐GQ1b antibody syndrome (AGS). Methods We conducted a retrospective observational study in all hospitalized patients in local public hospitals from January 2013 to December 2018. AGS was defined by hospitalized patients with positive serum anti‐GQ1b IgG, presumably encompassing Miller‐Fisher syndrome, Bickerstaff brainstem encephalitis and Guillain–Barré syndrome (GBS) variants. GBS cases were retrieved from the computerized database by diagnostic label. Campylobacter jejuni infection (CJI) injection was identified by positive stool culture. Monthly incidence rates of AGS, GBS and CJI were calculated. Poisson and negative binomial regression models with long‐term time trend were fitted to characterize the seasonal pattern. Results A total of 237, 572 and 2434 cases of AGS, GBS and CJI were identified, respectively, in a population of 7.3 million. The annual incidence rate of AGS was 0.54 per 100,000 person‐years. AGS was demonstrated to have an annual peak in the spring season, from March to April, which was congruent with that of GBS and slightly lagged the annual peak of CJI from February to March (likelihood ratio tests all p

Introduction: Data on local intraoperative anaphylaxis in Hong Kong is scarce, with few reviews available. We aimed to study the characteristics, presentations and workup results of cases referred to a local allergy clinic.Methods: A retrospective review was performed of patient referrals and workup results for suspected intraoperative anaphylaxis at Queen Mary Hospital drug allergy clinic in 2012-2016.Results: Tryptase was checked in only 81.7% (49/60) of the cases, most of which showed elevation (71.4%, 35/49). Among the 59 patients who received a workup, 47 (79.7%) showed positive findings, with a particularly high yield in the tryptase-positive subgroup (88.6%, 31/35). Among the 54 patients who consented to skin tests (the most sensitive investigation), 43 (79.6%) cases were positive. Overall, neuromuscular blockers were the commonest cause (25.0%, 15/60) of intraoperative anaphylaxis, while antibiotics ranked second (23.3%, 14/60). The timing of reactions was an important indication of potential allergens. For example, the majority of the neuromuscular blocker allergies occurred during the induction phase, while all gelofusine allergic events were in the maintenance phase of anaesthesia. 13 (21.7%) out of 60 cases received subsequent general anaesthesia procedures, with no recurrence of allergic reactions.Conclusion: Proper workup after an intraoperative anaphylactic event has a fairly good chance of identifying the causative allergen. These results are useful for patient management and the planning of subsequent anaesthetic procedures. [ABSTRACT FROM AUTHOR]