Diagnostic testing for galactose-alpha-1,3-galactose, United States, 2010 to 2018.

BACKGROUND: Alpha-gal syndrome (AGS) is an emerging immunoglobulin E (IgE)-mediated allergy to galactose-alpha-1,3-galactose (alpha-gal). The geographic distribution and burden of AGS in the United States are unknown. OBJECTIVE: To characterize alpha-gal IgE testing patterns and describe the trends and distribution from 2010 to 2018 in the United States. METHODS: This retrospective analysis included all persons tested for alpha-gal IgE antibodies by Viracor-IBT Laboratories (Lee's Summit, Missouri), the primary site of testing in the United States. Data included age and sex of person tested, specimen state of origin, collection date, and result value; persons with at least 1 positive test result (≥0.1 kU/L) were compared with negatives. Proportions tested and with positive test results were calculated using the US Census population estimates. RESULTS: Overall, 122,068 specimens from 105,674 persons were tested for alpha-gal IgE during July 1, 2010, to December 31, 2018. Nearly one-third (34,256, 32.4%) had at least 1 positive result. The number of persons receiving positive test results increased 6-fold from 1110 in 2011 to 7798 in 2018. Of those receiving positive test results, mean [SD] age was 46.9 (19.8) years; men were more likely to test positive than women (43.3% vs 26.0%). Arkansas, Virginia, Kentucky, Oklahoma, and Missouri had the highest number of persons who were tested and had a positive result per 100,000 population. CONCLUSION: More than 34,000 persons, most presumably symptomatic, have received positive test results for IgE antibodies to alpha-gal, suggesting AGS is an increasingly recognized public health problem. The geographic distribution of persons who tested positive is consistent with exposure to Amblyomma americanum ticks.

Evaluation of Two Enzyme-Linked Immunosorbent Assay Kits for Chikungunya Virus IgM Using Samples from Deceased Organ and Tissue Donors.

The identification of nearly 3,500 cases of chikungunya virus (CHIKV) infection in U.S. residents returning in 2014 and 2015 from areas in which it is endemic has raised concerns within the transplant community that, should recently infected individuals become organ and/or tissue donors, CHIKV would be transmitted to transplant recipients. Thus, tests designed to detect recent CHIKV infection among U.S. organ and tissue donors may become necessary in the future. Accordingly, we evaluated 2 enzyme-linked immunosorbent assays (ELISAs) for CHIKV IgM readily available in the United States using 1,000 deidentified serum or plasma specimens collected from donors between November 2014 and March 2015. The Euroimmun indirect ELISA identified 38 reactive specimens; however, all 38 were negative for CHIKV IgG and IgM in immunofluorescence assays (IFAs) conducted at a reference laboratory and, thus, were falsely reactive in the Euroimmun CHIKV IgM assay. The InBios IgM-capture ELISA identified 26 reactive samples, and one was still reactive (index ≥ 1.00) when retested using the InBios kit with a background subtraction modification to identify false reactivity. This reactive specimen was CHIKV IgM negative but IgG positive by IFAs at two reference laboratories; plaque reduction neutralization testing (PRNT) demonstrated CHIKV-specific reactivity. The IgG and PRNT findings strongly suggest that the InBios CHIKV IgM-reactive result represents true reactivity, even though the IgM IFA result was negative. If testing organ/tissue donors for CHIKV IgM becomes necessary, the limitations of the currently available CHIKV IgM ELISAs and options for their optimization must be understood to avoid organ/tissue wastage due to falsely reactive results.

Correlation of pneumococcal antibody concentration and avidity with patient clinical and immunologic characteristics.

PURPOSE: The quality of an antibody response is determined by both the concentration and the strength of antigen-binding, or avidity, of the antibodies produced. Currently, only antibody concentration is routinely evaluated in the clinical assessment of humoral immunity. Here we studied correlations of avidities and concentrations of antibodies to pneumococcal polysaccharides with immunologic and clinical characteristics of patients with recurrent infections. METHODS: We measured concentration and avidity of antibodies to 12 pneumococcal serotypes in 78 children aged 0.6-18 years with recurrent bacterial respiratory infections, and in 80 individuals who were being tested for peanut allergy, ages 0.4-15 years, serving as a comparison group. Avidity was assessed by measuring antibody binding in the presence of thiocyanate. RESULTS: Antibody concentrations and avidities correlated positively for very few types contained in the conjugated pneumococcal vaccine (PCV7) in both patients and controls with some dependence on age; there were even fewer correlations for non-PCV7 types. Antibody concentrations and avidities negatively correlated with age for most of the PCV7 types. There was no consistent correlation of total IgG or IgG subclasses with either concentrations or avidities. Overall, antibody concentrations were higher and avidities were lower in patients compared to controls. Patients requiring chronic antibiotic use tended to have higher antibody concentrations and lower avidities for most serotypes than patients who did not. We identified several patients having many infections with apparent good antibody concentrations with low avidity for many types. CONCLUSION: Antibody concentration and avidity correlate with patient clinical characteristics and distinguish patients from controls. Measurement of antibody avidity may provide another dimension for the clinical assessment of pneumococcal polysaccharide antibody response.

Autoantibodies in chronic idiopathic urticaria and nonurticarial systemic autoimmune disorders.

BACKGROUND: Chronic idiopathic urticaria (CU) has been associated with other autoimmune diseases and basophil-activating autoantibodies to FcεRI or IgE. It is unknown whether patients with systemicautoimmune diseases have a similar prevalence of these autoantibodies. OBJECTIVE: To compare the prevalences of basophil-activating autoantibodies (elevated CU Index) in patients with CU, rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Clinical characteristics and laboratory studies were examined for an association with the CU Index. METHODS: Adult patients, 27 with CU, 27 with RA, and 26 with SLE, and 20 healthy controls were compared on the basis of the CU Index panel, anti-IgE, and antithyroid antibodies. RESULTS: The CU Index values were significantly higher in the CU group when compared with the RA group but not when compared with the SLE group. 33% of CU, 23% of SLE, 3.7% of RA, and 15% of controls had apositive CU Index. Elevated antithyroid antibody levels did not correlate with a positive CU Index in any of the groups. An elevated CU Index in the SLE group was not associated with age, sex, ethnicity, disease severity, or history of atopy. CONCLUSION: The CU Index values were elevated in patients with CU and SLE. The presence of these autoantibodies did not correlate with disease activity or presence of thyroid antibodies. Functional autoantibodies may not be specific for chronic idiopathic urticaria, and their role in nonurticarial systemic autoimmune diseases requires further investigation.

Concomitant gene mutations of MBL and CYBB in chronic granulomatous disease: implications for host defense.

Chronic granulomatous disease (CGD) is associated with defective function of the NADPH-oxidase system in conjunction with phagocytic defects which leads to granuloma formation and serious infectious complications. This is often associated with significant morbidity and mortality. The association of defective phagocyte function with other coincidental immune defects is unknown. Defects in innate pathways seen with CGD, including complement systems, and toll-like and dectin receptor pathways, have not been described before. We present the case of a 2-year old male patient hospitalized with recurrent pneumonia, a non-healing skin ulcer, necrotizing lung granulomas, and epididymo-orchitis. Defective neutrophil chemiluminescence was detected by dihydrorhodamine (DHR) testing. Further evaluation demonstrated characteristic molecular mutations of CYBB consistent with CGD. Immune evaluation demonstrated polyclonal hyperglobulinemia, but a greatly reduced mannose binding lectin (MBL) level. Six biallelic polymorphisms in MBL gene and its promoter were analyzed using Light CyclerTM Real-time PCR assay. The LXPA/LYPB haplotype of MBL was detected in our patient; the latter is the defective haplotype associated with low MBL levels. Due to the implications for innate immunity and the protection against bacterial, viral, and fungal infections provided by MBL, a deficiency of this protein may have disastrous consequences on the long term outcomes of CGD. MBL deficiency can also complicate other disorders affecting the immune system, significantly increasing the risk of infection in such patients. Further studies looking at the frequency and implications of MBL deficiency in CGD are needed.

Comparison of the in vivo autologous skin test with in vitro diagnostic tests for diagnosis of chronic autoimmune urticaria.

Previous studies indicate that 30-50% of chronic urticaria patients have an autoimmune etiology. Clinical diagnosis of autoimmune urticaria is supported with the autologous serum skin test. The purpose of this study was to compare two laboratory tests for measurement of IgG autoantibodies to IgE or IgE receptors and compare the results with the autologous serum and plasma skin tests. We performed skin tests and two functional in vitro tests, basophil histamine release, and CD63 up-regulation to detect autoantibodies relevant to autoimmune urticaria. Both sera and citrated plasma were evaluated in the autologous skin test and histamine release assay. Thyroid autoantibodies were also measured. Basophils were incubated with patient plasma, sera, buffer, or anti-IgE. The cells were analyzed for CD63 expression and the supernatants were recovered for histamine analysis. There was high correlation between CD63 up-regulation and histamine release assays, but histamine release was more sensitive. There was a high concordance between sera and citrated plasma for the skin test. Sera from chronic urticaria patients produced higher mean histamine release (23%) compared with citrated plasma (12%). Thirty-one percent of patients positive in the histamine release assay were also positive for thyroid autoantibodies. This compares with 12% who were negative in the histamine release assay. These data show that in vitro basophil histamine release can be used to measure antibodies to FceRI, FceRII/CD23, or IgE and identify patients with autoimmune urticaria.