Humoral immunodeficiency does not appear to be associated with acute exacerbations in idiopathic pulmonary fibrosis patients (AE-IPF), according to a new article published in Lung.

The study found that only 6% of idiopathic pulmonary fibrosis (IPF) patients had serum immunoglobulins or IgG subclass levels below the lower limits of normal, while 13% of patients analyzed developed AE-IPF (4.7% per year).

The study also found that the immune response to pneumococcal polysaccharide vaccination was only severely impaired in 1% of patients. Elevated levels of lymphocytes in bronchoalveolar lavage (BAL) fluid were significantly associated with AE-IPF (P =.03).

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“Patients that did have immune defects were not more prone to develop AE-IPF. Contrarily, higher levels of lymphocytes in BAL fluid at the time of diagnosis were associated with the development of AE-IPF and shorter survival,” the authors said.

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Increased levels of other immune markers such as serum IgA (P =.01) and IgG (P =.04), BAL lymphocyte percentage (P =.005), and blood leukocyte (P =.01) and neutrophils (P =.0005) were all associated with worse survival. Only the lymphocyte count in BAL fluid remained statistically significant in a multivariate model, however.

A total of 409 patients diagnosed with IPF between 2011 and 2017 were included in this retrospective study. The patients were predominantly male (77%) with a median age of 68.2 years (range, 21–89 years).

Information on response to pneumococcal vaccination, BAL fluid samples, and immunoglobulin levels was not available for all patients. Baseline characteristics were not different between groups that had this information and those that did not, besides immunoglobulin levels, which were available more often in younger patients (P <.001).

A total of 47 patients experienced AE-IPF during the follow-up period and infection preceded these events in 28 (60%) of the patients. Of the patients who experienced AE-IPF, 89% had died and 3 had received lung transplants.

“The association between increased inflammatory markers and both AE-IPF and survival warrants further investigations. This local immune response in the lung may be a target for future therapies,” the authors concluded.


Hoffman TW, van Moorsel CHM, Kazemier KM, Biesma DH, Grutters JC, van Kessel DA. Humoral immune status in relation to outcomes in patients with idiopathic pulmonary fibrosis. Lung. Published online October 29, 2021. doi:10.1007/s00408-021-00488-w