# Associations of peripheral blood lymphopenia to disease course, treatment and TNF-α in sarcoidosis

## TL;DR

This study explores how low lymphocyte counts in blood relate to sarcoidosis disease progression, treatment response, and TNF-α levels.

## Contribution

The study identifies distinct patterns of lymphopenia and their association with TNF-α and treatment outcomes in sarcoidosis.

## Key findings

- PB total lymphopenia was present in 35% of sarcoidosis patients and was associated with a need for treatment.
- B-cell penia was the most common abnormality, occurring in 37% of patients.
- Lymphocyte counts increased in patients receiving TNF-α inhibitors, suggesting TNF-α's role in lymphopenia.

## Abstract

Severe sarcoidosis has been associated with peripheral blood (PB) total lymphopenia and high tumour necrosis factor α (TNF-α) levels, and the lymphopenia phenotype seems to respond poorly to conventional treatment. However, the mechanisms behind PB lymphopenia and its correlation with TNF-α levels remain unclear. Understanding the connections among PB lymphocyte subsets, TNF-α and clinical phenotype including treatment status could offer insights into how to individualize therapy.

PB samples from 65 consecutive sarcoidosis patients were collected at the Department of Respiratory Medicine, Karolinska University Hospital. Total lymphocyte, T-, B- and natural killer cell and TNF-α serum concentrations were measured and correlated to clinical parameters. Penias were defined as values below the lower limit of normal. The medical charts were retrospectively searched for the first PB total lymphocyte count, mostly recorded at time around diagnosis.

PB total lymphopenia was observed in 35% of patients, was present since time around diagnosis, and associated with a need for treatment later (p = 0.005). Lymphocyte counts did not change by therapy, except for an increase in patients receiving TNF-α inhibitors (TNFi) (p < 0.05).

B-cell penia, observed in 37% of patients, was the most common abnormality, also in patients with normal total lymphocyte counts, while T-cell penia mainly occurred in patients with total lymphopenia (91 vs 5%, p < 0.001).

B-cell penia is common in sarcoidosis patients while T-cell penia is mainly a feature of the sarcoidosis PB lymphopenia phenotype. Increased lymphocyte counts during TNFi treatment suggests that TNF-α signaling is of importance for sarcoidosis associated lymphopenia.

The online version contains supplementary material available at 10.1186/s12931-025-03212-x.