#00063238

39 years-old African American female presented with polyarthralgia and generalized weakness. Laboratory studies were remarkable for anemia (hemoglobin: 8.2g/dL), increased erythrocyte sedimentation rate 93 (normal < 20 mm/h) positive ANA titers; pANCA > 1:10,240 (normal < 1:20) and myeloperoxidase antibodies >8 (normal < 1).

The bone marrow was hypercellular for age, had trilineage hematopoiesis with myeloid hyperplasia (M:E ratio 3.4) with minimal dysmegakaryopoiesis (<10%) and dyserythropoiesis (6-7%) and with the aspirate smears notable for a subset of neutrophils, occasional monocytes and also eosinophils with large intracytoplasmic purple eosinophilic-like material, morphologically consistent with  “Lupus erythematosus” cells and variants. A flow cytometry analysis performed on a bone marrow aspirate sample detected 0.7% polytypic B-cells and 6.5% T-lymphocytes with a CD4 to CD8 cell ratio of 0.5. A T-cell receptor beta gene rearrangement was detected by PCR.  T-cell receptor gamma gene rearrangements were not detected. The karyotype was normal, and the MDS FISH panel was reported negative. The small clonal T-lymphoid population is favored to be reactive in nature as small clonal T-cell subsets can be identified in patients with autoimmune disorders [1].

In 1949, Dr. Hargraves described the “Lupus erythematosus” cells (LE cells) on a bone marrow study [2-3].  The classic LE cells are neutrophils that engulfed naked nuclei of dying cells in patients with lupus erythematosus, and were used in the classification criteria of systemic lupus erythematosus (SLE) until 1997. The study of Haserick and Bortz from 1949 demonstrated formation of LE cells in bone marrow preparations from healthy subjects when treated with plasma from patients with SLE, phenomenon also observed by Hargraves [2]. After several decades, and with the discoveries of current autoantibodies [5] research data demonstrated that the ANA antibodies bind the naked nuclei of apoptotic cells engulfed by phagocytotic cells [6]. With time, the LE cells have been identified not only in the bone marrows aspirate of patients with SLE but also in other body fluids (i.e. pleural fluid, synovial fluids etc). While most of the cases described neutrophils as LE cells, the phenomenon was also observed in monocytes, labeled as “tart” cells [7]. In our patient, occasional eosinophils with phagocytized nuclear material were also identified at close inspection, findings emphasizing the various types of myeloid cells capable of phagocytizing naked nuclear material in patients with autoimmune disorders. After her diagnosis, the patient is treated with prednisone for her ANCA positive rheumatologic disease.

1.     French LE, Lessin SR, Addya K, et al. Identification of Clonal T Cells in the Blood of Patients With Systemic Sclerosis: Positive Correlation With Response to Photopheresis. Arch Dermatol. 2001;137(10):1309–1313. doi:10.1001/archderm.137.10.1309

2.     Hargraves, M. M. 1949. "Production in vitro of the L.E. cell phenomenon; use of normal bone marrow elements and blood plasma from patients with acute disseminated lupus erythematosus." Proc Staff Meet Mayo Clin 24 (9):234-7.

3.     D'Andréa, A., D. L Peillet, C. Serratrice, P. A. Petignat, V. Prendki, J. L. Reny, and J. Serratrice. 2018. "Diagnosis of systemic lupus erythematosus by presence of Hargraves cells in eosinophilic pleural effusion: Case report." Medicine (Baltimore) 97 (42):e12871. doi: 10.1097/MD.0000000000012871.

4.     Haserick JR, Bortz DW. Normal bone marrow inclusion phenomena induced by lupus erythematosus plasma. J Invest Dermatol 1949;13:47–9.

5.      Dema B, Charles N. Autoantibodies in SLE: specificities, isotypes and receptors. Antibodies (2016) 5(1):2. doi:10.3390/antib5010002

6.     Schmidt-Acevedo, S., B. Pérez-Romano, and A. Ruiz-Argüelles. 2000. "'LE cells' result from phagocytosis of apoptotic bodies induced by antinuclear antibodies." J Autoimmun 15 (1):15-20. doi: 10.1006/jaut.2000.0381.

7.     Hargraves MM, Richmond H, Morton R. Presentation of two bone marrow elements: the “Tart” cell and the “L. E.” cell. Proc Staff Meet Mayo Clin. 1948; 23: 25-28