Detection of Newly Secreted Antibodies Predicts Nonrecurrence in Primary Clostridioides difficile Infection

Abstract

Background: Within eight weeks of primary Clostridioides difficile infection (CDI), as many as 30% of patients develop recurrent disease with the associated risks of multiple relapses, morbidity, and economic burden. There are no clear clinical correlates or validated biomarkers that can predict recurrence during primary infection. This study demonstrates the potential of a simple test for identifying hospitalized CDI patients at low risk for disease recurrence. Methods: Forty-six hospitalized CDI patients were enrolled at Emory University Hospitals. Serum and a novel matrix from circulating plasmablasts called " M edium E nriched for N ewly S ynthesized A ntibodies" (MENSA) samples were collected during weeks 1, 2, and 4. Antibodies specific for ten C. difficile antigens were measured in each sample Results: Among the 46 C. difficile -infected patients, nine (19.5%) experienced recurrence within eight weeks of primary infection. Among the 37 non-recurrent patients, 23 (62%; 23/37) had anti- C. difficile MENSA antibodies specific for any of the three toxin antigens: TcdB-CROP, TcdBvir-CROP, and/or CDTb. Positive MENSA responses occurred early (within the first 12 days post-symptom onset), including six patients who never seroconverted. A similar trend was observed in serum responses, but they peaked later and identified fewer patients (51%; 19/37). In contrast, none (0%; 0/9) of the patients who subsequently recurred after hospitalization produced antibodies specific for any of the three C. difficile toxin antigens. Thus, patients with a negative early MENSA response against all three C. difficile toxin antigens had a 19-fold greater relative risk of recurrence. Discussion: MENSA and serum levels of IgA and/or IgG antibodies for three C. difficile toxins have prognostic potential. These immunoassays measure nascent immune responses that reduce the likelihood of recurrence thereby providing a biomarker of protection from recurrent CDI. Patients who are positive by this immunoassay are unlikely to suffer recurrence. Early identification of patients at-risk for recurrence by negative MENSA creates opportunities for targeted prophylactic strategies that can reduce the incidence, cost and morbidity due to recurrent CDI.

<i>Clostridioides difficile</i> – a new name, the old problems with diagnosis and treatment

“…Небольшая часть антитела-секретирующих клеток мигрирует во вторичные лимфоидные органы и костный мозг, чтобы стать долгоживущими плазматическими клетками [64]. Выполнение теста на наличие антител к Cd, специфичных к любому из трех антигенов токсина (TcdB-CROP, TcdBvir-CROP и/или CDTb), на 2-й и 12-й день от возникновения клинических проявлений позволяет при положительном результате исследования выделить группу пациентов с низкой вероятностью рецидивирующего течения КДИ [20].…”

“…Достоверных критериев предсказания вероятности рецидива нет, а клинические факторы риска рецидива являются слабыми предикторами. Ни один из наиболее часто упоминаемых факторов риска, включая предыдущую госпитализацию, основное заболевание, возраст и предшествующее использование антибиотиков, не имеет ассоциированного относительного риска выше 2 [20].…”

MENSA, a Media Enriched with Newly Synthesized Antibodies, to Identify SARS-CoV-2 Persistence and Latent Viral Reactivation in Long-COVID

“…MENSA antibodies often appear prior to seroconversion and differ from serum antibodies, which confound results with the patient's entire historical microbial record. In prior studies, we have successfully used MENSA to diagnose acute Lyme disease, Clostridioides difficile, Streptococcus pneumoniae, and deep bone/tissue infections with Staphylococcus aureus 19,[23][24][25][26][27] . In all, the novel MENSA assay can successfully diagnose repeat bacterial and viral infections from a single blood sample even when serum antibody titers are extremely high, showing the assay's exceptional ability to resolve complexity of antibody signals.…”

Circulating antibody-secreting cells are a biomarker for early diagnosis in patients with Lyme disease

“…Measurement of the specific antibodies that ASC secrete requires: 1) collection of the ASC-containing peripheral blood mononuclear cells (PBMC) from a whole blood sample; 2) removal of potentially interfering serum antibodies; and 3) time in culture for the secretion of measurable quantities of ASCderived antibodies (24 (MENSA). The abundance of the new antibodies can be readily measured in high sensitivity immunoassay formats such as Luminex [18,19].…”