Interreader reliability in assessment of nailfold capillary abnormalities by beginners: pilot study of an intensive videocapillaroscopy training program.

OBJECTIVE: To test the learning curve of rheumatologists with different experience in videocapillaroscopy (VCP) attending an intensive training program focused on interpretation of the main capillary nailfold abnormalities, the scleroderma (systemic sclerosis, SSc) pattern, and the normal pattern, and to determine their interreader agreement with an experienced investigator. METHODS: Five investigators (1 senior, 1 junior, and 3 beginners) participated in the exercise. The study was composed of 2 steps. First, an independent investigator selected representative VCP images of normal patterns and capillary abnormalities. The second step included the training program, which ran 4 hours per day for 7 days. The senior rheumatologist taught investigators to recognize and interpret the normal pattern, the capillary abnormalities, and the different types of SSc pattern. These abnormalities were considered: homogeneously enlarged capillaries, giant capillaries, irregularly enlarged capillaries, microhemorrhages, neoangiogenesis, avascular areas, and capillary density. RESULTS: A total of 300 VCP images were read from all the investigators. Both κ values and overall agreement percentages of qualitative and quantitative assessments showed progressive improvement from poor to excellent from the beginning to the end of the exercise. The sensitivity and specificity of the participants in the assessment of SSc pattern at the last lecture session were high. CONCLUSION: Our pilot study suggests that after an intensive 1-week training program, novice investigators with little or no experience in VCP are able to interpret the main capillary abnormalities and SSc pattern and to achieve good interreader agreement rates.

Regulation of gut inflammation and th17 cell response by interleukin-21.

BACKGROUND & AIMS: Interleukin (IL)-21, a T-cell-derived cytokine, is overproduced in inflammatory bowel diseases (IBD), but its role in the pathogenesis of gut inflammation remains unknown. We here examined whether IL-21 is necessary for the initiation and progress of experimental colitis and whether it regulates specific pathways of inflammation. METHODS: Both dextran sulfate sodium colitis and trinitrobenzene sulfonic acid-relapsing colitis were induced in wild-type and IL-21-deficient mice. CD4(+)CD25(-) T cells from wild-type and IL-21-deficient mice were differentiated in T helper cell (Th)17-polarizing conditions, with or without IL-21 or an antagonistic IL-21R/Fc. We also examined whether blockade of IL-21 by anti-IL-21 antibody reduced IL-17 in cultures of IBD lamina propria CD3(+) T lymphocytes. Cytokines were evaluated by real-time polymerase chain reaction and/or enzyme-linked immunosorbent assay. RESULTS: High IL-21 was seen in wild-type mice with dextran sulfate sodium- and trinitrobenzene sulfonic acid-relapsing colitis. IL-21-deficient mice were largely protected against both colitides and were unable to up-regulate Th17-associated molecules during gut inflammation, thus suggesting a role for IL-21 in controlling Th17 cell responses. Indeed, naïve T cells from IL-21-deficient mice failed to differentiate into Th17 cells. Treatment of developing Th17 cells from wild-type mice with IL-21R/Fc reduced IL-17 production. Moreover, in the presence of transforming growth factor-beta1, exogenous IL-21 substituted for IL-6 in driving IL-17 induction. Neutralization of IL-21 reduced IL-17 secretion by IBD lamina propria lymphocytes. CONCLUSIONS: These results indicate that IL-21 is a critical regulator of inflammation and Th17 cell responses in the gut.