Background/Purpose:

Patients with systemic lupus erythematosus (SLE) have multiple innate and adaptive immune response abnormalities. It is unknown whether they play a key role in the development of infections, which was the aim of the present study. Until now, a tool to predict infections that encompasses the clinical and immunological features characteristic of SLE patients was lacking.

Methods:

A prospective cohort study of 55 SLE patients with less than 5 years since diagnosis was undertaken in a tertiary care center. Patients were prospectively followed up during a twelve-month period, looking for the primary outcome that was the development of infection, defined as the presence of characteristic clinical features with response to antibiotic treatment, with or without microbiological isolation. Severe infections were defined as those requiring hospital admission for at least 72 hrs, IV antibiotic treatment or causing death. We registered relevant clinical data and performed immunophenotyping by flow cytometry. We analyzed the number of neutrophil extracellular traps (NETs) and their LL-37 expression by confocal microscopy. Repeated measure analysis for the immunosuppressive therapy, mean adjusted SLEDAI score for disease activity. Relative risks (RR) for infection adjusted for clinical and immunological features. The study was approved by the institutional ethics and research committees.

Results:

During 12 months of follow-up, 18 patients (32%) presented 19 infectious events in a median time of 21.5 weeks (IQR 4-24), 12% were severe. The main causes of infection were community-acquired pneumonia (23%), superior respiratory tract (23%) and urinary tract infections (17%), herpes zoster virus (17%), gastroenteritis (11%) and cellulitis (5%). In comparison to their baseline immunological parameters, there was a higher expression of LL-37 in LPS induced NETs and a higher amount of LDGs during the infectious events. After univariate and multivariate analysis, we developed an index to predict infection in SLE patients assigning a score according to the RR absolute values. The index parameters were cyclophosphamide use, absolute numbers of B cells, total Th17 lymphocytes and expression of TLR2 in monocytes measured with multi-parametric flow cytometry. We validated the index retrospectively in a nested case-control study and at baseline. In the case-control analysis, a score ≥2 was able to predict infection in the following 3 months (AUC= 0.79; likelihood ratio = 2.22, P=0.015). The same cutoff point at baseline predicted infection in the following year (AUC= 0.84; likelihood ratio = 2.0, P=0.012).

Conclusion:

Our compound clinical-immunological index is able to predict the development of infection in SLE patients, taking into account the use of cyclophosphamide, absolute numbers of peripheral Th17 and B cells as well as TLR2 expression in monocytes. By alerting clinicians about patients who are more prone to develop infections, there could be a closer follow-up of these patients, with a targeted, multidisciplinary approach.

ACR Meeting Abstracts - https://acrabstracts.org/abstract/a-predictive-clinical-immunological-index-for-infections-unveils-novel-innate-and-adaptive-immunity-abnormalities-as-key-risk-factors-for-infections-in-a-cohort-of-patients-with-systemic-lupus-erythem/