Infection may occur repeatedly in some patients leading to recurrent hospitalizations, high healthcare utilization, and poor quality of life [4]. B IgA antibodies at baseline and at day 3 for ICH subjects, with a notable difference in concentrations of antitoxin B IgA at day 3 (ICH, 6.7 ELISA units [IQR, 1.913.9] compared with non-ICH, 18.1 ELISA units [IQR, 4.931.7];P= .003). == Conclusions == The ICHs with CDI demonstrated lower levels ofC difficileantitoxin antibodies in serum and stool during early CDI therapy compared with non-ICHs. These data provide insight into the humoral response to CDI in IMR-1A ICHs. Keywords:C difficiletoxins,Clostridioides difficileinfection, humoral immunity, immunosuppression Immunocompromised patients with CDI demonstrated lower levels ofClostridioides difficiletoxin-specific antibodies in the serum and stool at treatment day 3 compared with non-immunocompromised subjects. These data provide insight into the natural history of CDI humoral response in immunocompromised subjects. Clostridioides difficileis the leading cause of healthcare-associated infectious diarrhea. More than 450 000 cases and 20 000 associated deaths have been reported in the United States annually [13].Clostridioides difficileinfection (CDI) presents with a spectrum of clinical disease ranging from mild, self-limited diarrhea to a fulminant colitis. Infection may occur repeatedly in some patients leading to recurrent hospitalizations, high healthcare utilization, and poor quality of life [4]. Certain patient populations such as the elderly and patients with weakened immune systems appear to be at an enhanced risk for CDI and its complications [511]. The increased risk for CDI in immunocompromised hosts (ICHs) may be multifactorial and due to external clinical factors, such as antibiotic exposure and immunosuppressing agents, as well as intrinsic host factors including impaired specific humoral responses toC difficiletoxins A and B. Prior research in non-immunocompromised host populations (non-ICH) has suggested that the magnitude of antibody responseto C difficiletoxin A may protect against symptomatic CDI and recurrence [12]. In addition, serum antitoxin B antibody response has been associated with protection from recurrent CDI (rCDI) [13]. Although it is possible that these immunologic markers may also be of utility in ICH patient populations, data are lacking due to the exclusion of ICH patients from many studies. The aim of this research was to evaluate the humoral immune response toC difficiletoxins A and B in a cohort of immunocompromised patients. Our goal was to better understand whether impaired humoral immunity specific toC difficiletoxins influences clinical symptoms and risk of rCDI. Our central hypothesis was that impairment inC difficile-specific antibody response toC difficiletoxins A IMR-1A and B may drive host risk for CDI and influence clinical outcomes in immunocompromised patients. The importance of this research is 2-fold. First, a more complete understanding of the immune response toC difficiletoxins is necessary to help predict whether future therapies such as aC IMR-1A difficilevaccine might work to prevent disease or recurrence in this population. Second, the data will help to inform future passive immunization strategies targeting this patient population. == METHODS == == Patient Cohorts == Inpatients at Beth Israel Deaconess Medical Center ([BIDMC] Boston, MA) and Texas Medical Center ([TMC] Houston, TX) were prospectively enrolled between June 2016 and February 2020. Eligible subjects were 18 years old with positive stoolC difficilenucleic acid amplification test (NAAT) result, initiating CDI therapy, and had acute diarrhea, defined as follows: (1) 3 unformed bowel movements (UBMs) during any 24 hours in the 48 hours before or the 24 hours after the time of stool collection; (2) persistent diarrhea in the same time window, per multiple provider notes; or (3) pseudomembranous colitis or (4) in IMR-1A patients with chronic diarrhea, a clear change in stool consistency IKBKB antibody or frequency. In most cases definition 1 was applied. Patients were excluded for the following: history of chronic diarrhea without acute exacerbation, presence of colostomy, receipt of bezlotoxumab, intravenous immunoglobulin (Ig) or fresh frozen plasma within 30 days, enrollment in anyC difficilevaccine study, >48 hours of CDI therapy, insufficient stool specimen, or stool sample older than 72 hours. TheC difficiletesting method at BIDMC was NAAT only (before July 2018) (GeneXpert real-time polymerase chain reaction; Cepheid) and NAAT with.