Amyloid arthropathy associated with multiple myeloma: a systematic analysis of 101 reported cases.

OBJECTIVE: Amyloid deposition in multiple myeloma (MM) may lead to an arthropathy resembling rheumatoid arthritis (RA). Since a systematic description of its natural history is lacking, we have performed a systematic analysis of all published cases. METHODS: Literature review featuring backward and forward database searches and direct inspection of reference lists. Inclusion criteria were as follows: publication between 1931 and 2012, diagnosis of multiple myeloma, and demonstration of light chain amyloid (AL) in any organ or in synovial fluid, arthritis, or synovitis. RESULTS: Overall, 101 cases were identified. Median age was 59 years and the male-to-female ratio was 1:1. A systemic manifestation of MM was reported in 88 cases. In 53 of these, characteristic physical findings (carpal tunnel syndrome, macroglossia, shoulder pad, and soft tissue swelling/masses) were present. Arthritis manifested before the diagnosis of MM in 63 cases, with 33 cases initially misdiagnosed as RA. There were 72 cases of poly-, 17 of oligo-, and three of monoarthritis. The shoulder joint was most commonly affected, followed by knees and small hand joints. Median synovial fluid leukocyte count was 2460 cells/mm(3), and was normal in seven cases. Synovial histopathology often featured mild synovitis without plasma cell infiltration. Imaging revealed articular or periarticular inflammation in many cases and bone lesions near 22% of affected joints. Treatments varied but led to some improvement in the majority of cases. CONCLUSIONS: These results solidify previous experience that MM arthropathy tends to feature a symmetric RF-negative nonerosive polyarthritis. However, the results also highlight the diversity of its presentations and stress the importance of arthropathy as a potentially under-recognized presenting manifestation of MM.

Inhibition of autophagy through MAPK14-mediated phosphorylation of ATG5.

Autophagy is a catabolic mechanism that is important for many biological processes such as cell homeostasis, development and immunity. Though many molecular components of the autophagy pathway have been identified, the signaling pathways regulating the activity of essential autophagy mediators are still poorly defined. We recently demonstrated that the mitogen-activated protein kinase MAPK14 (p38α), when activated by the GADD45B (Gadd45ß)-MAP3K4 (MEKK4) signaling complex (but not other MAPK14 activators), is directed to autophagosomes. Therefore, we demonstrated for the first time that MAPK14 operates at this subcellular compartment. Importantly, activation of MAPK14 impairs autophagosome-lysosome fusion and, thus, autophagy. This was demonstrated by increased autophagic flux in MAPK14-deficient as well as in GADD45B-deficient cells. Moreover, we identified a novel post-translational modification of the crucial autophagy mediator ATG5, since MAPK14 directly phosphorylates ATG5 at threonine 75, which is evolutionarily conserved from yeast to human. Using ATG5-deficient cells, which we reconstituted with either a phosphorylation-defective or a phospho-mimetic mutant of ATG5, we demonstrated that phosphorylation of ATG5 results in impaired autophagy.

Friendship jealousy in young adolescents: individual differences and links to sex, self-esteem, aggression, and social adjustment.

Children's vulnerability to jealousy surrounding their best friends was explored in 2 studies. Study 1 involved 94 adolescents who reported on their friendship jealousy on a newly created measure. Results indicated that the jealousy measure had sound psychometric properties and produced individual differences that were robust over time and free from socially desirable responding. As expected, girls and adolescents with low self-worth reported the greatest friendship jealousy. Study 2 involved 399 young adolescents and extended the measurement of self-report jealousy to a broader age range. In addition, Study 2 included assessments of jealousy provided by friends and other peers. Self- and peer-reported jealousy were only modestly associated and had somewhat distinct correlates. Structural modeling revealed that young adolescents' reputation for friendship jealousy was linked to behaving aggressively and to broader peer adjustment difficulties. Both self- and peer-reported jealousy contributed to loneliness.