Human Lymph Node Stromal Cells Have the Machinery to Regulate Peripheral Tolerance during Health and Rheumatoid Arthritis.

BACKGROUND: In rheumatoid arthritis (RA) the cause for loss of tolerance and anti-citrullinated protein antibody (ACPA) production remains unidentified. Mouse studies showed that lymph node stromal cells (LNSCs) maintain peripheral tolerance through presentation of peripheral tissue antigens (PTAs). We hypothesize that dysregulation of peripheral tolerance mechanisms in human LNSCs might underlie pathogenesis of RA. METHOD: Lymph node (LN) needle biopsies were obtained from 24 RA patients, 23 individuals positive for RA-associated autoantibodies but without clinical disease (RA-risk individuals), and 14 seronegative healthy individuals. Ex vivo human LNs from non-RA individuals were used to directly analyze stromal cells. Molecules involved in antigen presentation and immune modulation were measured in LNSCs upon interferon γ (IFNγ) stimulation (n = 15). RESULTS: Citrullinated targets of ACPAs were detected in human LN tissue and in cultured LNSCs. Human LNSCs express several PTAs, transcription factors autoimmune regulator (AIRE) and deformed epidermal autoregulatory factor 1 (DEAF1), and molecules involved in citrullination, antigen presentation, and immunomodulation. Overall, no clear differences between donor groups were observed with exception of a slightly lower induction of human leukocyte antigen-DR (HLA-DR) and programmed cell death 1 ligand (PD-L1) molecules in LNSCs from RA patients. CONCLUSION: Human LNSCs have the machinery to regulate peripheral tolerance making them an attractive target to exploit in tolerance induction and maintenance.

Malignant giant cell tumor in the carpal tunnel: a case report and review of literature.

Background Malignant tenosynovial giant cell tumors (GCTs) are extremely rare, and their etiology is unknown. However, this type of malignancy is associated with high metastasis and mortality rates. Therefore, the treatment of choice is wide excision. Case Description A 66-year-old man complained of tingling and loss of sensation in the left hand, caused by a tumor that compressed the median nerve. The tumor was excised. Histopathologic examination revealed a ganglion cyst. Two years later, the patient visited our clinic with recurrent and similar complaints of the left hand. This time, however, the lesion turned out to be a malignant tenosynovial GCT and was treated by amputation of the forearm. Literature Review Since 1979, only 37 malignant tenosynovial GCTs have been reported in literature. Follow-up of these patients showed that 11 patients died of the disease, 4 patients were still living with the disease, and 14 patients had no evidence of disease after treatment. The other seven patients were lost to follow-up, and one patient died of other causes. In these 37 patients, a high incidence of lymph node metastasis (41%) and a high mortality rate (30%) were seen. Clinical Relevance Although this malignant tenosynovial GCT is very rare, high mortality rates have been observed because of the high incidence of lymph node metastases. Therefore, more awareness has to be created, to recognize and treat this tumor timely.