Objective:

To identify cellular immune signatures for infection risk using routine laboratory tests.

Background:

Monoclonal anti-CD20 therapies increase risk for infection in patients with multiple sclerosis (MS). Our previous work identified female sex, BMI, age, serum IgG, and complete B cell suppression as risk factors for infection in MS patients who received anti-CD20 therapy.

Design/Methods:

We performed a database search of patients seen at Stanford between 2015-2023 who received anti-CD20 infusions and completed a chart review for bacterial or viral infections that developed after starting treatment. We identified patients that had complete blood count (CBC) and T- and B-lymphocyte subsets (FLOW) before and after the first infusion. We performed one-way repeated measures MANOVAs to assess differences in CBC or FLOW data over time between bacterial, viral, and no infection groups.

Results:

We included MS patients (n=292, mean age 45.0y, SD 13.7y) with FLOW (n=119) and CBC (n=85) data. 76 (26%) and 108 (37%) patients developed bacterial and viral infections after initiation of therapy, respectively. Among bacterial, viral, and no infection groups, there was reduction in FLOW absolute lymphocyte and CD3+ cells (bacterial: F=19.6, viral: F=28.9, p=<0.001) over time. Similarly, CBC absolute lymphocyte, neutrophil, and immature granulocyte counts decreased over time (bacterial: F=8.1, viral: F=6.4, p=<0.001). To our surprise, post hoc analyses revealed a greater reduction in neutrophil count in the no infection group compared to the bacterial group (F=8.3, p=0.005), as well as greater reduction in absolute lymphocytes and CD3+ cell counts in the no infection group compared to the viral group (lymphocytes: F=4.8, p=0.031; CD3: F=5.0, p=0.028).

Conclusions:

In MS patients on anti-CD20 therapy, immune cell counts declined after treatment differentially among patients who had bacterial, viral, or no infection. Unexpectedly, those with infections had higher immune cell counts, likely from the body’s attempt to fight infection.