MUM1 (multiple myeloma oncogene 1)/IRF4 (interferon regulatory factor 4) gene has been identified as an oncogene transcriptionally activated by t(6;14)(p25;q32) chromosomal translocation in multiple myeloma (MM).
Psoriatic arthritis (PsA) is a chronic inflammatory skin disease that causes enthesitis and destructive arthritis and significantly lowers patient quality of life. Recognition of the two target organs (the skin and joints) involved in the immunopathophysiology of PsA helped in elucidating the pathology of various systemic autoimmune diseases targeting multiple organs. Recent advances in immunology and genetics have made it clear that acquired immunity, especially that mediated by the Th17/IL-23 axis, plays an important role in the inflammatory pathology observed in psoriasis and PsA. Additionally, involvement of natural immunity has also been suggested. Microbial infection has been known to trigger psoriasis and PsA. Recent clinical studies using biopharmaceuticals, such as tumor-necrosis-factor- (TNF-) α inhibitors and IL-12/23 p40 antibodies, indicate that studies need not be based only on the immunological phenomena observed in PsA pathology since disease pathology can now be verified using human-based science. Considering this aspect, this paper discusses the immunopathology of PsA compared to psoriasis (cutaneous) and rheumatoid arthritis in humans and immunopathology of PsA with respect to the Th17/IL-23 axis and microbial infection.
Chromosomal band 1p34-36 is a commonly rearranged locus in many types of cancers. We cloned the breakpoint region of a chromosomal translocation, t(1;14)(p34;q32), found in the human multiple myeloma (MM) cell line, ODA. This rearrangement occurred between the nearby switch region of the immunoglobulin heavy chain (IgH) gene (Sc3) at 14q32 and the first intron of the human retinoic acid-inducible E3 protein (E3)/lysosomeassociated protein, transmembrane-5 (LAPTm5) gene at the 1p34 locus. Consequently, the E3 gene, which is a hematopoietic cell-specific transcript induced by retinoic acid and located at the rearranged allele, was interrupted within its coding region and was not expressed in the ODA cell line in spite of the other allele still being intact. The expression derived from the remaining intact allele in ODA cells was silenced by DNA methylation at sequences within the first intron around a GC-rich EagI site. Interestingly, the silenced expression of E3 mRNA due to DNA methylation of intron 1 sequences was frequently encountered in MM cells [6/10 (60%) of MM cell lines tested], while E3 is expressed in normal plasma cells and in most other hematopoietic cell lines including those of B-cell lineage. Thus, as the E3 protein has been suggested to be involved in cellular differentiation and apoptotic pathways in certain cell types, our results suggest that loss of E3 gene expression might be a crucial event during the progression of human MM.
There are several case reports of systemic vasculitis associated with chronic suppurative lung diseases. We describe a 46-year-old female, previously diagnosed as having diffuse panbronchiolitis (DPB), presenting with hemosputum and dyspnea. Her serum titer of MPO-ANCA was positive together with a high titer of BPI-ANCA. Chest X-ray and chest CT scan showed pulmonary hemorrhage, and the renal biopsy specimen revealed necrotizing, crescentic glomerulonephritis. She was diagnosed as having ANCA-associated vasculitis, and more specifically, microscopic polyangiitis accompanied by DPB. She was treated with methylprednisolone pulse therapy, followed by intravenous cyclophosphamide. This case suggested a possible association with chronic bacterial infection, which may play a role in the pathogenesis of ANCA-associated vasculitis.
Monthly minodronate is more acceptable and may be more effective than weekly alendronate or risedronate for prevention and treatment of bone loss in patients with systemic rheumatic diseases on glucocorticoid therapy.
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