A personal history of pneumonia, intestinal infection, gonorrhea, septicemia, herpes zoster, pyelonephritis, cystitis, sinusitis, rhinitis, influenza, meningitis, Lyme disease, pericarditis, myocarditis, endocarditis, empyema, and erysipelas was also associated with a significantly increased risk of MGUS

A personal history of pneumonia, intestinal infection, gonorrhea, septicemia, herpes zoster, pyelonephritis, cystitis, sinusitis, rhinitis, influenza, meningitis, Lyme disease, pericarditis, myocarditis, endocarditis, empyema, and erysipelas was also associated with a significantly increased risk of MGUS. an asymptomatic, pre-malignant plasma cell disorder, preceding multiple myeloma (MM) and related disorders, including Rabbit polyclonal to Aquaporin2 Waldenstr?ms macroglobulinemia and amyloid light-chain (AL) amyloidosis (1, 2). MGUS is usually characterized by monoclonal immunoglobulins (M-protein) 3.0 g/dL, bone marrow plasma cell infiltration 10%, and the absence of hypercalcemia, renal insufficiency, anemia, or bone lesions (CRAB criteria). Furthermore, a free light chain (FLC) ratio between 0.26 and 1.65 and a urinary protein 500 mg/24 hours is required (Table?1) (10). MGUS is present in around 3-4% of the general population over the age of 50 and around 6% of those over the age of 70 (11, 12). All MM cases are preceded by MGUS (13, 14). However, only a small proportion of CB-184 individuals with MGUS ever progresses to a malignant disease, with an annual risk of progression from MGUS to MM of around 1% (2). Table?1 Autoimmune diseases associated with MGUS. thead CB-184 th valign=”top” align=”left” rowspan=”1″ colspan=”1″ CB-184 Autoimmune disease /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Number of studies showing significant associations /th th valign=”top” align=”center” rowspan=”1″ colspan=”1″ Number of studies showing no associations /th /thead Total autoimmune diseases3 (3C5)CAutoantibodies detectable3 (3C5)C?Systemic involvement3 (3C5)C?Rheumatoid arhritis2 (3, 5)1 (6)*?Systemic sclerosis3 (3C5)1 (6)*?Sj?gren syndrome3 (3, 7, 8)2 (5, 6)*?Polymyositis/dermatomyositis2 (5, 8)3 (3, 4, 6)*?Kikuchi disease1 (7)COrgan involvement3 (3C5)C?Discoid lupus erythematous1 (9)2 (3, 6)*?Neuromyelitis optica1 (7)C?Autoimmune thrombocytopenia2 (3, 8)C?Autoimmune hemolytic anemia1 (4)1 (3)?Pernicious anemia3 (3C5)1 (6)*?Guillian-Barr syndrome1 (3)C?Celiac disease1 (3)C?Chronic rheumatoid heart disease1 (3)CAutoantibodies not detectable2 (3, 4)1 (5)?Ankylosing spondylitis4 (3C5, 7)1 (6)*?Vitiligo1 (8)C?Polymyalgia rheumatica1 (3)C?Giant cell arteritis1 (3)C?Aplastic anemia1 (3)C Open in a separate window Cindicates not applicable. *indicates that the study is based on a screened population. An intermediate stage between MGUS and MM is usually smoldering multiple myeloma (SMM), characterized by a serum M-protein 3.0 g/dL or a urinary M-protein 500 mg per 24 hours and/or a clonal bone marrow plasma cell infiltration of 10-60%, in the absence of end-organ damage (CRAB) or an involved:uninvolved serum FLC ratio of 100 or 0.01, and with 1 focal lesions on magnetic resonance imaging (MRI) (10). In SMM, the annual risk of progression to malignancy is usually 10% in the first 5 years, 3% in the following 5 years and CB-184 1% after that (15). Predicting which MGUS patients will progress to malignancy has proved challenging. Current risk stratification models stratify MGUS-patients into four risk categories based on three risk factors: serum M-protein concentration 15 g/L, non-IgG isotype, and an FLC ratio 0.26 or 1.65. The presence of all three risk factors is considered high-risk MGUS, with a 58% combined 20-year risk of progression, without death accounted for as a competing risk. Conversely, absence of all risk factors is considered low-risk MGUS, with a 5% 20-year risk of progression (16). In MGUS, as well as MM, the M-protein is usually secreted by post-germinal center plasma cells that have undergone somatic hypermutation, antigen selection, and immunoglobulin heavy-chain (IgH) class-switch recombination (17, 18). Various known genetic factors distinguish clonal plasma cells in MGUS, SMM and MM from healthy plasma cells; however, distinguishing the clonal plasma cells in MGUS from those in MM has proven more difficult. Overexpression of certain miRNA expression patterns have been detected by MM cell lines and tumors, but not in MGUS; however, more analyses are needed before these patterns can be effectively used to distinguish MGUS from MM tumors (18). Additionally, some shared cytogenic abnormalities (CAs) are found in MGUS and MM, including IgH-translocations, aneuploidy, and chromosome 13q deletion, but how they affect the development of MGUS has not been established (18). Nevertheless, certain CAs have been linked with higher risk of progression compared with.