Detection of antinuclear antibodies: recommendations from EFLM, EASI and ICAP.

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.

Good's syndrome in a patient with cytomegalovirus retinitis.

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.

Solid tumors subsequent to arsenic trioxide treatment for acute promyelocytic leukemia.

Arsenic trioxide (As(2)O(3)) is highly efficacious for acute promyelocytic leukemia (APL). Environmental arsenic exposure predisposes to malignancies, but the risk for therapeutic arsenic is undefined. Three APL patients (de novo, 2; therapy-related, 1) in a cohort of 59 cases given oral-As(2)O(3) for induction and maintenance treatment developed secondary cancers (nasopharyngeal carcinoma, 2; colonic adenocarcinoma, 1) at 16, 36 and 55 months post-As(2)O(3) therapy. Retrospective analysis of biomarkers (Epstein Barr virus serology and quantification, carcinoembryonic antigen) showed the potential presence of cancers before or shortly after As(2)O(3) therapy, suggesting that As(2)O(3) had not initiated these malignancies. Compared against matched background population, there was an increased risk of second cancer (p=0.012, standard incidence ratio=6.5; 95% confidence interval=1.4-19.0).

The correlation among obesity, apnea-hypopnea index, and tonsil size in children.

BACKGROUND: The correlation between obesity and severity of obstructive sleep apnea (OSA) is well established in adults, but data are inconsistent in children. We hypothesized that there is a significant correlation between the degree of obesity and the severity of OSA in children. METHODS: We retrospectively reviewed records of weight, height, history, and polysomnography of all 1- to 15- year-old children referred to our sleep laboratory. Children with known anomalies and repeated polysomnography were excluded from this study. Obesity was defined as body mass index z score (BMI Z score) > 1.96. The correlation between BMI Z score and apnea-hypopnea index (AHI) was assessed. Possible confounding factors, ie, age, gender, and tonsil size, were adjusted by multiple linear regression. RESULTS: Four hundred eighty-two children were included in this study. Obese children had a significantly higher AHI (median, 1.5; interquartile range [IQR], 0.2 to 7.0) than the AHI of nonobese children (median, 0.7; IQR, 0.0 to 2.5). BMI Z score was significantly correlated with log-transformed AHI (Ln[AHI]) [r = 0.156, p = 0.003]. BMI Z score and tonsil size were still correlated with Ln(AHI) even after adjusted for other confounding factors (p = 0.001). CONCLUSION: Degree of obesity as measured by BMI Z score and tonsil size are significantly related to severity of OSA as reflected by the AHI, although the correlation is mild.

The interferon gamma gene polymorphism +874 A/T is associated with severe acute respiratory syndrome.

BACKGROUND: Cytokines play important roles in antiviral action. We examined whether polymorphisms of IFN-gamma,TNF-alpha and IL-10 affect the susceptibility to and outcome of severe acute respiratory syndrome (SARS). METHODS: A case-control study was carried out in 476 Chinese SARS patients and 449 healthy controls. We tested the polymorphisms of IFN-gamma,TNF-alpha and IL-10 for their associations with SARS. RESULTS: IFN-gamma +874A allele was associated with susceptibility to SARS in a dose-dependent manner (P < 0.001). Individuals with IFN-gamma +874 AA and AT genotype had a 5.19-fold (95% Confidence Interval [CI], 2.78-9.68) and 2.57-fold (95% CI, 1.35-4.88) increased risk of developing SARS respectively. The polymorphisms of IL-10 and TNF-alpha were not associated with SARS susceptibility. CONCLUSION: IFN-gamma +874A allele was shown to be a risk factor in SARS susceptibility.