Bone marrow findings in rheumatoid arthritis patients with peripheral cytopenias

Abstract

Objective The aim was to study bone marrow (BM) cellularity, morphological characteristics, and types of cellular infiltrates in rheumatoid arthritis (RA) patients associated with peripheral cytopenias. Background RA is a systemic, autoimmune disease leading to joint destruction. BM is an important compartment in RA, where there are autoreactive lymphocytes, abnormal production of cytokines, and abnormal BM microenvironment, which may affect the integrity of the BM and accordingly may require specific modalities in treatment. Patients and methods In the current study, we examined 60 RA patients with cytopenias (defined according to WHO as hemoglobin level below 12 g/dl (woman), 13 g/dl (man), platelet count below 150×109/l, absolute neutrophil count below 1.8×109/l, and lymphocytes below 1.0×109/l. The diagnosis of RA was made according to the American College of Rheumatology (2010) criteria. All patients were subjected to thorough history taking, physical examination, imaging studies including abdominal ultrasound, and chest radiography and laboratory investigations including routine investigations, blood film, antinuclear antibody, antidouble stranded DNA antibody, rheumatoid factor, anticyclic citrullinated peptide (anti-CCP) antibody, and BM aspiration and biopsy. Flow cytometry immunophenotyping was performed to detect lymphocytic infiltration in the BM and its subtypes. Results The patients were predominantly women (91.7%); 40 (66.6%) patients had normocellular BM, 16 (26.6%) patients had hypercellular and four (6.6%) patients had hypocellular BM. Dysmyelopoiesis was present in five (8.3%) patients; dyserythropoietic and megaloblastoid changes were present in 26 (43.3%) patients whereas dysmegakaryopoiesis was present in six (10%) patients. BM eosinophils mean±SD was 2.95±1.51%. BM plasma cell mean±SD was 4.0±2.35. BM lymphocytes mean±SD was 15.65±6.75% and was predominantly T-lymphocytes (mean±SD: 61.63±8.69%). BM-activated (CD25+) T-lymphocytes mean±SD was 23.8±11.5. Higher BM lymphocytes, T-cells, and plasma cell percentages were statistically associated with increased frequencies of positive anti-CCP, neutropenia, thrombocytopenia, and arthritis and were positively correlated to inflammatory markers (erythrocyte sedimentation rate, C-reactive protein, and ferritin).The percentage of activated (CD25+) BM T-lymphocytes was higher in RA patients with either positive C-reactive protein, positive anti-CCP, elevated ferritin, or pancytopenia. There was no significant relation between lymphocytic infiltration (either B-lymphocyte or T-lymphocyte) and type of BM cellularity. Conclusion Lymphocytic infiltration, especially T-lymphocytes is closely related to the activity markers in RA and to the type and degree of cytopenia in RA patients.

Keywords

• bone marrow
• cytopenia
• rheumatoid arthritis