CD4+ T cells could be key in treating RA-associated lung disease

Rheumatoid arthritis (RA)-associated lung disease is different from idiopathic pulmonary fibrosis, researchers say, pointing to an increased number of CD4+ T cells. A new study in the January 2005 issue of Arthritis & Rheumatism suggests that CD4+ T cells are critical for the development of pulmonary manifestations in RA and may have implications for the treatment of lung disease.

“These findings may be of major importance to our understanding of the nature of RA-associated lung disease,” write the researchers, led by Dr Carl Turesson (Mayo Clinic College of Medicine, Rochester, MN and Malmo University Hospital, Sweden). “Our data also suggest that despite similarities in the radiographic and histopathologic appearance, there are fundamental differences in the pathophysiologic patterns between RA-associated interstitial pneumonitis (IP) and idiopathic usual and nonspecific IP.”Turesson and colleagues studied paraffin-embedded lung biopsy specimens from 31 patients with and without RA who had a diagnosis of either nonspecific IP or usual IP. A pathologist who was blinded to the clinical data reviewed tissue sections. The researchers found that age and pulmonary-function test results were similar in RA and non-RA patients. After high-temperature antigen unmasking, the investigators incubated sections with mouse monoclonal antibodies directed against CD3, CD4, CD8, CD16, and CD20. The group coded all slides and obtained digital images of the entire tissue area. They quantified staining using a computer-assisted image analysis.Drugs that suppress T-cell activation may be useful treatmentTuresson and his team found that staining for CD4 was more prominent in patients with RA than in the non-RA comparison group (median 9.3 cells/mm2, interquartile range 5.5-27.3 vs 0.6 cells/mm2, interquartile range 0.2-1.9; p=0.002).They also found that CD4+ cell counts were increased in RA patients with nonspecific IP as well as in RA patients with usual IP, with no major difference between these groups. The researchers found that the results were similar for quantification of CD3 (p=0.012). And they observed a less striking trend toward more CD8+ cells in RA patients (p= 0.27 vs those with non-RA lung disease).”This is a rationale for trying newer approaches to treating RA lung disease that involve drugs that block T-cell action. That might help us make progress against this disease,” Turesson said in a news release. “Many doctors who have seen our results say, ‘This is what I’ve always believed.’ But no one had proved it to them. Our work provides the evidence that was lacking, so from that standpoint, it is a very helpful demonstration that hopefully will lead to the development of new treatment strategies for RA lung disease.”The researchers point out that patients with RA were more likely to be receiving treatment with glucocorticosteroids at the time of lung biopsy than patients with idiopathic IP. They note that while steroids would be expected to reduce lymphoid infiltrates, this would, if anything, tend to diminish differences in the number of cells positive for CD4 and other markers between the RA group and the non-RA group. They argue that treatment differences therefore cannot explain their results.Turesson and colleagues add that their patient selection was done without matching, but the age distribution and pulmonary-function test results were similar between the RA group and the control group. “Although our sample size was small,” they continue, “the ratio of women to men of 1.5:1 in the RA group is compatible with an overall 2- to 3-fold increase in the incidence of RA in women compared with men and is consistent with a suggested association between male sex and lung disease in patients with RA.”(Source: Arthritis Rheum 2005; 52:73-79: Joint and Bone: January 2005.)