Background: Basophil activation tests (BATs) are useful in identifying culprits of perioperative anaphylaxis (PA), but their utility remains limited due to technical limitations, cost, and availability. Being able to prioritize patients with likely higher yields for BAT would be useful in reducing costs and manpower. Objective: We sought to investigate whether tryptase levels and clinical parameters may be useful for selecting patients for BATs. Methods We performed a 10-year retrospective study in Hong Kong to investigate the performance of BATs associated with tryptase levels (taking during PA) and other clinical parameters. Results: Of 90 patients, 70 (77.8%) showed significant tryptase level elevation and 37 (41.1%) had a positive BAT result. BAT-positive patients presented with significantly higher absolute levels (15.9 mu g/L vs 9.1 mu g/L; P = .018), absolute elevation (12.8 mu g/L vs 7.1 mu g/L; P = .012), and fold elevation (5.6- vs 4.1-fold; P = .014) of acute tryptase than did BAT-negative patients. Among patients with positive BAT result, 94.6% (35 of 37) demonstrated elevated acute tryptase, significantly more than the BAT-negative group (66.0%; P < .001). In regression analysis, tryptase elevation was the sole significant factor correlated to BAT positivity (odds ratio, 10.14; 95% CI, 2.15-47.85; P = .003). Overall, elevated acute tryptase demonstrated a sensitivity of 94.7% and a negative predictive value of 90.0% in predicting positive results with BATs. Conclusions: We observed that tryptase elevation is a very sensitive predictor of BAT positivity among patients with identified culprits of PA. Acute elevation of tryptase would not only aid in confirming anaphylaxis but may also help guide the decision toward selecting labor-intensive and costly in vitro tests such as BATs.

OBJECTIVES:Antinuclear antibodies (ANA) are important for the diagnosis of various autoimmune diseases. ANA are usually detected by indirect immunofluorescence assay (IFA) using HEp-2 cells (HEp-2 IFA). There are many variables influencing HEp-2 IFA results, such as subjective visual reading, serum screening dilution, substrate manufacturing, microscope components and conjugate. Newer developments on ANA testing that offer novel features adopted by some clinical laboratories include automated computer-assisted diagnosis (CAD) systems and solid phase assays (SPA).METHODS:A group of experts reviewed current literature and established recommendations on methodological aspects of ANA testing. This process was supported by a two round Delphi exercise. International expert groups that participated in this initiative included (i) the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Working Group "Autoimmunity Testing"; (ii) the European Autoimmune Standardization Initiative (EASI); and (iii) the International Consensus on ANA Patterns (ICAP).RESULTS:In total, 35 recommendations/statements related to (i) ANA testing and reporting by HEp-2 IFA; (ii) HEp-2 IFA methodological aspects including substrate/conjugate selection and the application of CAD systems; (iii) quality assurance; (iv) HEp-2 IFA validation/verification approaches and (v) SPA were formulated. Globally, 95% of all submitted scores in the final Delphi round were above 6 (moderately agree, agree or strongly agree) and 85% above 7 (agree and strongly agree), indicating strong international support for the proposed recommendations.CONCLUSIONS:These recommendations are an important step to achieve high quality ANA testing.

Background: Studies on perioperative anaphylaxis (PA) in Asia are lacking. Furthermore, allergy workup for PA has largely been limited to the "silver standard" of skin tests (ST). Using in vitro tests as an adjunct to ST may improve and overcome these diagnostic challenges.Objective: To evaluate the clinical characteristics and diagnostic tests of patients with suspected PA through the Perioperative Anaphylaxis Workup Study in Hong Kong cohort.Methods: Patients with a diagnosis of PA over a 10-year period were recruited into the Perioperative Anaphylaxis Workup Study in Hong Kong. We reviewed the medical records, tryptase elevation, and diagnostic tests including ST, specific immunoglobulin E, and basophil activation tests (BAT).Results: In 151 patients with PA, diagnosis was reached in three-fourths of the cases (113/151, 74.8%). The most common culprits identified were neuromuscular blocking agents (25.8%), b lactams (17.2%) and chlorhexidine (13.9%). Severe anaphylaxis was associated with female sex, older age, elevated acute tryptase levels, and more cardiovascular manifestations during induction. Skin tests remained the most sensitive diagnostic modality overall (66.2%). BAT showed better performance for chlorhexidine and gelofusine anaphylaxis, with sensitivity of 80.0% and 79.6%, respectively. Specific Immunoglobulin E indicated even higher sensitivity (95.2%) than did ST (85.0%) and BAT (80.0%) for chlorhexidine anaphylaxis but performed poorly for other drugs. Conclusion: Neuromuscular blocking agents remain the most common culprit in PA. There was a higher prevalence of gelofusine anaphylaxis in our cohort than was seen in the literature. Skin tests remain the most sensitive testing modality. In vitro tests for chlorhexidine and gelofusine showed promising results, but more studies to further elucidate its use are warranted.& COPY; 2023 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

BACKGROUNDPeanut allergy is common in Chinese children, yet the most predictive diagnostic cut-offs for skin prick test (SPT) and blood testing in this population are unclear.OBJECTIVESWe aimed to determine the optimal cut-off values for whole-peanut SPT, specific IgE (sIgE) and component-resolved diagnostics (CRD) for Chinese children based on outcomes of open oral food challenges (OFC) to peanut.METHODSWe recruited ethnic-Chinese patients 1-18 years old who were suspected of having peanut allergy based on a history of reactions after exposure or sensitization although peanut naïve. Considering the AUC value of 0.8, 80% power and 5% level of significance with two tails, 26 patients were needed. Sensitivities, specificities, positive and negative predictive values, and receiver operating characteristic curves (ROCs) and their area-under-curves (AUCs) for SPT, peanut sIgE, and CRD were compared.RESULTSThirty-one subjects participated. Only SPT reached statistical significance (AUC 0.91, p = 0.0001), but not the other tests. Seven retrospective data were added to optimize the power. SPT remained to be the best predictor, followed by Ara h 2 sIgE (AUC 0.72, p = 0.02). An SPT wheal size of 3 mm and Ara h 2 sIgE of 0.14 kU(A)/L yielded the highest Youden's index. The specificity of SPT and Ara h 2 sIgE reached 94% at 6 mm and 0.74 kU(A)/L, respectively. Comparisons of ROCs revealed that SPT was significantly better than Ara h 2 sIgE (p = 0.03) and whole-peanut sIgE (AUC 0.61, p = 0.26).CONCLUSIONIn Chinese children, SPT appeared to be the best predictor for peanut allergy, followed by Ara h 2 sIgE.

We report a heterozygous, 2,009 base pairs (bps) genomic DNA deletion within the SERPING1 gene that has not previously been reported in a case of type I hereditary angioedema (HAE). The patient is a 28-year-old Han Chinese female living in Hong Kong who has suffered from recurrent angioedema since adolescence, with increasing attack frequency as she entered adulthood; in the past, episodes occurred annually, but now occur every two to three months. The affected areas are not itchy and include common sites such as the left and right forearms, but without throat involvement. The patient also experiences epigastric pain. The patient's mother suffers from similar symptoms. A mutation in the serine protease inhibitor, clade G, member 1 (SERPING1) gene is associated with HAE. Patients with HAE type I commonly carry either a small deletion within SERPING1 or a truncated transcript. We performed a multiplex ligation-dependent probe amplification (MLPA) assay on our indexed patient. Our result suggests a 2,009 bps deletion spanning across exons 5 and 6 within SERPING1. Although earlier literature has described other large DNA deletions encasing exons 5 and 6 in SERPING1, these DNA rearrangements were larger in size between 4 and 6 kbps, and the breakpoint locations were generally not determined due to technical constraints (Pappalardo et al., 2000; Duponchel et al., 2001; Roche et al., 2005; Loules et al., 2018; and Göβwein et al., 2008). Our report describes mapping of this 2,009 bps in SERPING1. Using a combination of molecular techniques, we were able to confirm and locate this large heterozygous genomic DNA deletion that includes both exons 5 and 6 of SERPING1.

Natural killer (NK) cell cytotoxic function is critical in guarding an organism against viral infections and malignantly transformed cells. Although the 51Chromium (51Cr)-release assay is regarded as the gold standard for assessing NK cell cytolytic activity, this method is associated with a number of technical problems including the use of radioactive reagents and inconsistent assay performance, due to the lack of assay standardisation across laboratories. Here we describe the setup of a flow cytometry (FC) based method for the measurement of NK cell cytotoxicity, suitable for patient testing. The FC protocol was assessed using four normal samples, and reference values for NK activity of the local Hong Kong population were defined by 40 peripheral blood samples from healthy volunteers. For method validation, we tested a total of 13 specimens including nine healthy individuals and four patients with clinical conditions that were expected to have NK cell dysfunction. We directly compared those results between FC and the 51Cr-release assay and we were able to demonstrate that FC is a clinically valid method for measuring NK cell function in a clinical setting.

Autoimmune encephalitis is an important group of disease that can mimic infectious encephalitis, with one of the most severe forms being meningoencephalomyelitis. One of the recently identified biomarkers, glial fibillary acidic protein (GFAP), targets the cytosolic intermediate filament protein of astrocytes and causes a variety of clinical symptoms. Here, we report an adult Chinese woman presented with acute onset of confusion, CSF lymphocytosis, markedly elevated total protein mimicking tuberculosis meningitis with rapid deterioration resulted in coma and respiratory failure. She was diagnosed with anti-GFAP meningoencephalomyelitis, which later developed tetraplegia, sensorineural hearing loss, brainstem, bulbar and respiratory dysfunction. Intravenous immunoglobulin and methylprednisolone resulted in partial improvement. Further immunotherapy with plasma exchange and rituximab resulted in marked recovery.

Aim: The study aims to analyze the incidence, clinical features, investigation findings and treatment outcomes of anti-N-methyl-D-aspartate receptor encephalitis in children from Hong Kong. Method: A retrospective study was carried out on paediatric patients diagnosed with anti-NMDAR encephalitis in Hong Kong from January 2009 to December 2015. Results: Fifteen patients (67% female, 93% Chinese) were identified over seven years and the estimated incidence in Hong Kong was 2.2/million children per year (95% CI 1.2-3.6). The median age of presentation was 12 years (range 1-17 years). The most common symptom groups observed were abnormal psychiatric behavior or cognitive dysfunction (14/15, 93%) and seizures (14/15, 93%), followed by speech dysfunction (13/15, 87%), movement disorders (12/15, 80%), decreased level of consciousness (10/15, 67%) and autonomic dysfunction or central hypoventilation (5/15, 33%). The median number of symptom groups developed in each patient was 5 (range 3-6). All patients were treated with intravenous immunoglobulin and/or steroids. Three patients (20%) with more severe presentation required additional plasmapheresis and rituximab. Outcome was assessable in 14 patients. Among those eleven patients who had only received intravenous immunoglobulin and/or steroids, nine patients (82%) achieved full recovery. One patient (9%) had residual behavioral problem, while another one (9%) who developed anti-NMDAR encephalitis after herpes simplex virus encephalitis was complicated with dyskinetic cerebral palsy and epilepsy. Among those three patients who required plasmapheresis and rituximab, one (33%) had full recovery and two (66%) had substantial recovery. The median duration of follow up was 20.5 months (range 3-S4 months). Conclusion: Anti-NMDAR encephalitis is an acquired, severe, but potentially treatable disorder. Ethnicity may play a role in the incidence of anti-NMDAR encephalitis and we have provided a local incidence with the majority of patients being Chinese. The diagnosis of anti-NMDAR encephalitis should be considered in children presenting with a constellation of symptoms including psychiatric and neurological manifestations. Patients may respond to first line immunotherapy. For those who do not, second line therapy is indicated in order to achieve a better outcome. (C) 2018 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Beta-lactam hypersensitivity is important in clinical practice. It is generally believed that skin-test hypersensitivity decreases with time and resensitisation after tolerated application is rare.

Haemolytic uraemic syndrome (aHUS) is a rare thrombotic microangiopathy characterised by haemolysis, platelet consumption and renal injury. Eculizumab is monoclonal anti-C5 antibody that is proven to be useful in its management.

Background There are no data on neutralising antibodies to interferon-beta and its clinical implications in Chinese patients with multiple sclerosis (MS). Objectives The objectives of this study were to investigate the prevalence of neutralising antibodies among Chinese patients with relapsing MS receiving interferon-beta (1a or 1b) and to study the association between neutralising antibodies and the clinical-radiological response. Methods We performed a cross-sectional study on MS patients who received interferon-beta for 9 months or more, and evaluated the clinical response by relapses and magnetic resonance imaging lesions. Blood samples were evaluated for myxovirus resistance protein A (MxA) gene expression by polymerase chain reaction, anti-interferon-beta binding antibodies by enzyme-linked immunosorbent assay, and neutralising antibodies by cell-based MxA protein induction and luciferase reporter gene assays. Assay performances were evaluated by receiver operating characteristic analysis. Results Among 78 subjects recruited, 61/77 (79%) had anti-interferon-beta binding antibodies, and 22/78 (28%) had neutralising antibodies by MxA protein induction assay. The presence of high-titre neutralising antibodies was associated with poor clinical outcome (odds ratio 6.1, 95% confidence interval 1.5–25.6, P = 0.013). The sensitivity and specificity for neutralising antibodies using MxA gene expression assay (cut-off 0.20) was 80% and 68%, respectively (area under the curve 0.71). Conclusions Neutralising antibodies are associated with poor clinical outcome in Chinese patients with relapsing MS. MxA gene expression and protein induction assays are complimentary assays for neutralising antibody detection.

To investigate the etiology and prevalence of optic neuritis in a Chinese population. This was a single centre prospective cohort study. Consecutive patients with either a first or recurrent attack of optic neuritis from November 2010 to December 2011 were recruited from a district hospital in Hong Kong Special Administrative Region, China. All patients underwent serology testing for NMO (neuromyelitis optica) IgG; oligoclonal bands from lumbar puncture; computer tomography and contrast magnetic resonance imaging (MRI) of the brain and orbit as well as visual field; and optical coherence tomography testing. Patients were followed up for 1 year after the initial attack. 30 optic neuritis subjects were recruited. 73.3 % (22/30) remain as clinical isolated syndrome (CIS) after 1-year follow-up. 10 % (3/30) patients developed multiple sclerosis. 10 % (3/30) were diagnosed with NMO and 6.7 % (2/30) with NMO-spectrum disorder. The majority of acute unilateral optic neuritis in Chinese was CIS in origin although a fraction does progress to develop MS or NMO-related disorders. Clinicians should be aware of the associations and offer appropriate systemic workups.

Recipients of influenza A (H1N1) vaccine in 1976 had an increased risk for the neurologic disorder Guillain-Barré syndrome (GBS). Anti-ganglioside antibodies, which might be associated with the development of GBS, were previously reported to be induced in mice immunized with an H1N1 vaccine of 1976 or another influenza vaccine. In this study we analyzed anti-ganglioside antibodies in human subjects infected with or vaccinated against 2009 pandemic H1N1, including eight patients diagnosed to have post-vaccination GBS. Antibodies against GM1 or another ganglioside were not detected in any subject or in vaccinated mice. Our results did not support the induction of anti-ganglioside antibodies by influenza viruses or vaccines.

Because of the rarity of dural sinus thrombosis in children with polycythaemia vera (PV), the options for diagnosis and treatment remain elusive. A 12-year-old girl was admitted with dural sinus thrombosis associated with PV, diagnosed by magnetic resonance venography. She was managed with interventional endovascular thrombolectomy and venoplasty, phlebotomy, hydroxyurea, low molecular weight heparin, and aspirin followed by warfarin. She made a good recovery without residual neurological deficit. This case highlights the importance of diagnosis and appropriate intervention with multi-modality treatments in patients with PV and thrombosis.

OBJECTIVE:To provide a synopsis of current thalassaemia major patient care in Hong Kong.DESIGN:Retrospective study.SETTING:All haematology units of the Hospital Authority in Hong Kong.PATIENTS:All patients with thalassaemia major with regular transfusion.RESULTS:To date, there were 363 thalassaemia major patients under the care of the Hospital Authority. Prenatal diagnosis has helped to reduce the number of indigenous new cases, but in recent years immigrant cases are appearing. The patients have a mean age of 23 (range, 1-52) years, and 78% of them are adults. In 2009, they received 18 782 units of blood. This accounted for 9.5% of all blood consumption from the Hong Kong Red Cross. In the past, cardiac iron overload was the major cause of death (65%) and few patients survived beyond the age of 45 years. The availability of cardiac iron assessment by magnetic resonance imaging (T2 MRI) to direct the use of oral deferiprone chelation has reduced the prevalence of heart failure and cardiac haemosiderosis, which should reduce mortality and improve life expectancy.CONCLUSION:The future for thalassaemia care in Hong Kong is bright. With better transfusion and chelation, it should be possible to avoid growth and endocrine deficiencies in younger patients.

ABSTRACTThe majority of patients with pandemic influenza H1N1 2009 had mild illness, but some, including those with no risk factors for severe disease, may succumb to this infection. Besides viral factors such as the D222/225G substitution of the hemagglutinin, host factors such as IgG2 subclass deficiency recently was reported to be associated with severe disease in a cohort of Australian patients besides other known risk factors, including underlying chronic illness, extremes of age, and pregnancy. We conducted a case-control study of 38 Asian patients with respiratory failure due to severe pandemic influenza and compared the results to those for 36 mild cases. None had selective IgG2 deficiency, but the level of IgG2 subclass was significantly lower in the severe cases (3.55 g/liter versus 4.75 g/liter;P= 0.002), whereas the levels of IgG1, IgG3, and IgG4 were not significantly different from those of the mild cases. Previous studies suggested that some IgHG2 and FcγRIIa genotypes were associated with IgG2 deficiency. The allelic frequency of the IgHG2 genotypes in our severe cases was not correlated with their levels of IgG2, while that of FcγRIIa was not significantly different from that of the general Han Chinese population (P= 0.216). Only the overall cytokine/chemokine profile (P= 0.029) and serum globulin level (P= 0.005) were found to be independently associated with the IgG2 level by multivariate analysis. The lower IgG2 level in our severe group might be related to cytokine dysregulation rather than being a significant risk factor for severe pandemic influenza. The importance of this finding for therapeutic intervention will require further studies of larger cohorts of patients.

Thymoma-related adult-onset immunodeficiency or Good's syndrome is an uncommon condition. This case, of a 50-year-old woman who was human immunodeficiency virus-negative and developed herpes zoster and severe cytomegalovirus retinitis 6 months after removal of a thymoma, is the first to be reported in Hong Kong. Immunological investigations revealed no B cells, hypogammaglobulinaemia, a low CD4 count, and a low CD4/CD8 ratio. We recommend that immunological investigations, including T-cell subsets, B cells, and quantitative immunoglobulins, should be part of the routine diagnostic evaluation of patients with thymoma and infections.

Thymic atrophy and the progressive immune decline that accompanies it is a major health problem, chronically with age and acutely with immune injury. No solution has been defined. Here we demonstrate that one of the three mesenchymal cell subsets identified by single-cell analysis of human and mouse thymic stroma is a critical niche component for T lymphopoiesis. The Postn+ subset is located perivascularly in the cortical-medullary junction, medulla and subcapsular regions. Cell depletion demonstrated that it recruits T competent cells to the thymus and initiates T lymphopoiesis in vivo. This subset distinctively expresses the chemokine Ccl19 necessary for niche functions. It markedly declines with age and in the acute setting of hematopoietic stem cell transplant conditioning. When isolated and adoptively transferred, these cells durably engrafted the atrophic thymus, recruited early T progenitors, increased T cell neogenesis, expanded TCR complexity and enhanced T cell response to vaccination. These data define a thymus lymphopoietic niche cell type that may be manipulated therapeutically to regenerate T lymphopoiesis.