Background/Purpose:

Large granular lymphocyte (LGL) proliferations can be observed in some auto-immune disorders, especially rheumatoid arthritis. However, reports of LGL proliferations in primary Sjogren’s syndrome (pSS) are extremely rare. We here described the main characteristics and outcome of 9 patients presenting LGL proliferation in the context of pSS.

Methods:

All patients from the reference centre for systemic autoimmune diseases (in particular for pSS) diagnosed with pSS (ACR/EULAR 2016 criteria) and having a LGL proliferation were included. LGL proliferations were characterized by blood lymphocyte immunophonetyping and their TCR clonality by PCR. Clinical data and outcome were analyzed for all patients.

Results:

Nine pSS patients (8 women; median age of 67 [range 52 to 87] years) were diagnosed with LGL proliferation. All but one had active disease at the time of LGL diagnosis (median ESSDAI 11 [range 6 to 35]). Two patients had a history of lymphoma, one developed LGL proliferation under chemotherapy and the other in the context of an indolent and untreated lymphoma. In 8/9 patients, LGL proliferations were T-CD8 (T-LGL), and only one was of NK-type (NK-LGL). LGL proliferation was monoclonal in 4/9 and oligoclonal in 4/9 (data missing for patient with NK-LGL proliferation). A STAT3 mutation was searched in 2 patients and was negative in both. Neutropenia was the main reason for searching for a LGL proliferation ; neutrophil count was < 1500/mm3 in 7/9 and < 500/mm3 in 3/9 patients. At diagnosis, median lymphocyte cell count was 1120/mm3 (range 480 to 7250) and median LGL cell count was 440/mm3 (range 150 to 6000) representing 23% (range 13 to 64%) of the total lymphocyte count.

Interestingly, 6 patients had received Rituximab (for lymphoma in 2, for pSS systemic manifestations or cryoglobulinemia in 4). The median time between LGL proliferation diagnosis and first Rituximab injection was 7 months (range 15 days to 13 months). Neutropenia occurred in 5/6 patients having received RTX. One patient with neutropenia, was retreated with Rituximab for a cryoglobulinemia relapse. Neutropenia occurred after the first injection (1200/mm3) and even worsened after the second (700/mm3).

In 2 patients, severe neutropenia required treatment by G-CSF which only led to transient efficacy between the injections. Methotreaxate was added in these 2 patients and allowed normalization in one case whereas neutrophil count partly improved in the other case. Spontaneous remission occurred in 1/7 patients and non-severe neutropenia persisted in 4/7 others at last evaluation.

Conclusion:

This is one of the largest study analyzing LGL proliferation in pSS. As in other auto-immune diseases, LGL were mainly T-LGL, their main feature is neutropenia and they were observed in patients with high activity. Interestingly, the majority occurred in patients treated by Rituximab and could have a link with this treatment. This study suggest that neutropenia occurring after Rituximab treatment in patients with lymphoma or systemic auto-immune disease (but rarely in patients with rheumatoid arthritis) could be the consequence of a minimal LGL proliferation that should be searched in this context.

« Back to 2018 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/large-granular-lymphocyte-proliferations-in-primary-sjogrens-syndrome-an-iatrogenic-manifestation/