Defect in Automated Antigen Excess Detection Discovered after Reviewing Serum Free Light Chain Results in Context with Clinical Findings.

Serum κ and λ free light chains can be markedly elevated in monoclonal gammopathies; consequently, serum free light chain (sFLC) immunoassays are susceptible to inaccuracies caused by antigen excess. As a result, diagnostics manufacturers have attempted to automate antigen excess detection. A 75-year-old African-American woman had laboratory findings consistent with severe anemia, acute kidney injury, and moderate hypercalcemia. Serum and urine protein electrophoresis and sFLC testing were ordered. The sFLC results initially showed mildly elevated free λ light chains and normal free κ. The pathologist noted that sFLC results were discrepant with the bone marrow biopsy, electrophoresis, and immunofixation results. After manual dilution of the serum, repeat sFLC testing revealed significantly higher λ sFLC results. Antigen excess causing falsely low sFLC quantitation may not be detected by immunoassay instruments as intended. Correlation with clinical history, serum and urine protein electrophoresis results, and other laboratory findings is essential when interpreting sFLC results.

The clinical features of overlap syndrome (ANCA-associated crescentic glomerulonephritis [AACGN] and immune complex-mediated glomerulonephritis) are similar to those of AACGN alone.

The overlap syndromes of anti-neutrophil cytoplasmic antibodies (ANCA)-associated crescentic glomerulonephritis (AACGN) and variants of immune complex medicated glomerulopathy (ICMGN) have been reported. But very few have compared AACGN alone with the overlap syndromes (AACGN plus ICMGN). The aim of this retrospective study was to make that comparison, following serum creatinine (sCr) to determine whether the two groups (AACGN-only group versus overlap group) would behave differently over time. We identified 14 cases with dual diagnoses of AACGN and various ICMGN in the overlap group. Data were collected and compared with 15 randomly selected AACGN-only cases over the similar period of time. The overlap syndrome represented 0.35% of our overall biopsies (14/4049). All 14 patients were ANCA positive and had crescentic formation. The percentage of crescents in the biopsies ranged from 10 to 78%. ICMGN included the following: membranoproliferative glomerulonephritis, post-infectious glomerulonephritis, membranous glomerulopathies, idiopathic mesangial proliferative glomerulonephritis, lupus nephritis, and IgA nephropathy. With the exception one biopsy revealing lupus nephritis class III, most of the ICMGN were mild. When compared to the AACGN-only group, there were no significant differences in clinical and histologic indices including age, percent of crescents, and sCr (on biopsy days, and over the follow-up periods), although the numbers of follow-up cases were limited over time. Our findings suggest that AACGN was the dominant disease process in the majority of overlap syndromes between AACGN and ICMGN, similar to the clinical processes of AACGN-only disease, therefore, the AACGN in overlap syndrome cases should be the main target for clinical management.

Longitudinal characterization of the IgM and IgG humoral response in symptomatic COVID-19 patients using the Abbott Architect.

BACKGROUND: Antibody testing has recently emerged as an option to assist with determining exposure to SARS-CoV-2, the causative agent of COVID-19. Elucidation of the kinetics and duration of the humoral response is important for clinical management and interpreting results from serological surveys. OBJECTIVES: Here we evaluated the clinical performance of Abbott SARS-CoV-2 IgM and IgG assays, as well as the longitudinal dynamics of the antibody response in symptomatic COVID-19 patients. STUDY DESIGN AND RESULTS: The diagnostic specificity was 100 % for IgM and 99.67 % for IgG using 300 pre-COVID-19 serum specimens. Using 1349 sequential serum samples collected up to 168 days post symptom onset from 427 PCR-confirmed individuals, clinical test sensitivity of the SARS-CoV-2 IgM assay was 24.6 % at ≤7 days, 75.3 % at 8-14 days, 95.0 % at 15-21 days, and 96.0 % at 4-5 weeks (peak test sensitivity). The median duration of time for IgM seroconversion was 10 days. IgM levels declined steadily 4-5 weeks after symptom onset, and the positive rate dropped to 30.8 % at >3 months. The diagnostic sensitivity for the SARS-CoV-2 IgG assay post symptom onset was 23.2 % at ≤7 days, 69.5 % at 8-14 days, 93.6 % at 15-21 days, and 99.6 % at 4-5 weeks (peak test sensitivity). The median duration of time for IgG seroconversion was 11.5 days. During the convalescent phase of the infection, a decline in the IgG level was observed in patients who were followed for >100 days. Despite that decline, 92.3 % of the patient cohort remained IgG positive 3-6 months following symptom onset. CONCLUSIONS: This study demonstrates the Abbott IgM assay against SARS-CoV-2 is detected slightly earlier compared to IgG, with both tests exhibiting excellent overall sensitivity and specificity. In symptomatic patients who test negative by PCR for a SARS-CoV-2 infection, assessing IgM and IgG antibodies can aid in supporting a diagnosis of COVID-19.