Abstract
The role of the humoral immune response to Clostridium difficile in modulating the severity of C. difficile infection (CDI) is unclear. We compared the levels of serum immunoglobulin G (IgG) and immunoglobulin A (IgA) against toxin A (TcdA) and toxin B (TcdB) of C. difficile between CDI and control patients and according to disease severity. The levels of IgG and IgA antibodies against TcdA and TcdB were measured in sera from patients with CDI (n = 50; 19 had severe CDI) and control patients (n = 52), using ELISA. Patients with CDI had higher levels of IgG antibodies against TcdA and TcdB than controls (p = 0.001 and p = 0.04, respectively). Higher IgG levels against TcdA and TcdB were found in patients with mild vs. severe CDI 7–14 days after the diagnosis (p = 0.004 and 0.036, respectively). A factor analysis included both IgA and IgG levels against both toxins into one composite variable, which was of higher values in patients with mild vs. severe CDI (p = 0.026). In conclusion, the systemic humoral immune responses against TcdA and TcdB might modulate the severity of CDI. These preliminary findings provide a basis for future large-scale studies and support the development and evaluation of active and passive immunotherapies for CDI management.
Highlights
Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients [1,2]
Patients with C. difficile infection (CDI) had significantly higher geometric mean titers (GMTs) values of serum immunoglobulin G (IgG) antibody against TcdA compared to the control group: 20.1 ELISA units (EUs) (SD 2.5) vs. 11.6 EU (SD 2.1), p = 0.001, and against TcdB: 18.0 EU (SD 2.6) vs. 12.0 EU (SD 2.7), p = 0.04
A significantly higher GMT of serum immunoglobulin A (IgA) antibodies against TcdB was found among CDI patients with mild disease compared to patients with severe disease 9.2 EU (SD 2.7) vs. 4.9 EU (SD 1.8), p = 0.023
Summary
Clostridium difficile is the most common cause of infectious diarrhea in hospitalized patients [1,2]. C. difficile can cause asymptomatic colonization, as well as disease with various degrees of severity from mild diarrhea to fulminant colitis and death [6,7,8] Such variability in the outcome of C. difficile infection can be attributed to the patient’s characteristics, including advanced age, the severity of underlying comorbidities, and the systemic humoral immune response against C. difficile toxins [9,10,11,12]. Secondary analysis of the placebo group in these trials showed an inverse association between high endogenous antibody titers against TcdB but not TcdA and recurrent CDI [19] Despite this evidence, there are unresolved questions, namely the relationship of the humoral immune responses against C. difficile toxins with the disease severity of CDI and the relative importance of serum antibodies against toxins TcdA and TcdB. The evaluation of the humoral immune responses according to the severity of CDI is novel, compared to previous studies that mostly focused on the prevention and recurrence of CDI
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