Faculty Bibliography

PURPOSE: To compare and assess subregional, compartmental, and whole T1rho values of menisci in patients with doubtful-minimal (Kellgren-Lawrence [KL] grade 1-2) as compared to moderate-severe (KL3-4) osteoarthritis (OA) and healthy controls at 3 Tesla (T). MATERIALS AND METHODS: Forty-six subjects were included in the study and subdivided into three subgroups: 16 healthy controls (4 females, 12 males; mean age = 34.4 +/- 10.2 years; age range, 24-63 years), 20 patients with doubtful-minimal (KL1-2) OA (9 females, 11 males; mean age = 61.9 +/- 10.8 years; age range, 40-80 years), and 10 patients with moderate-severe (KL3-4) OA (4 females, 6 males; mean age = 71.1 +/- 9.6 years; age range, 58-89 years). All subjects were evaluated on a 3T MR scanner using a spin-lock-based three-dimensional GRE sequence for T1rho mapping. Clinical proton density (PD)-weighted fast spin echoes (FSE) images in the sagittal (without fat saturation), axial, and coronal (fat-saturated) planes were acquired for cartilage Whole-Organ MR Imaging Score (WORMS) grading. Analysis of covariance was performed to determine whether there were any statistically significant differences between subregional, compartmental, and whole T1rho values of meniscus among healthy controls, OA patients with KL1-2 and with KL3-4. RESULTS: Lateral anterior (median +/- interquartile range: 26 +/- 3 ms) and medial posterior (29 +/- 6 ms) meniscus subregions in healthy controls had significantly lower T1rho values (P < 0.05) than the corresponding meniscus subregions in both KL1-2 (29 +/- 7 ms and 35 +/- 8 ms, respectively) and KL3-4 (30 +/- 12 ms and 40 +/- 13 ms, respectively) OA subjects. Significantly lower meniscus T1rho values (P < 0.05) were also identified in the medial compartment in healthy controls (28 +/- 5 ms) relative to both KL1-2 OA subjects and KL3-4 OA subjects (32 +/- 7 ms and 37 +/- 7 ms, respectively). The entire meniscus T1rho values in healthy controls (28 +/- 4 ms) were significantly lower than those of both KL1-2 and KL3-4 OA subjects (33 +/- 6 ms and 34 +/- 6 ms, respectively). CONCLUSION: Significant elevations of T1rho values in specific regions of menisci in both KL1-2 and KL3-4 OA patients indicate that T1rho mapping may be sensitive to meniscus degeneration. The preliminary results suggest that damage in the medial posterior subregion and medial compartment of menisci may possibly be associated with osteoarthritis. J. Magn. Reson. Imaging 2013. (c) 2013 Wiley Periodicals, Inc.

BACKGROUND: Age, gender and genetic predisposition are major intrinsic risk factors for osteoarthritis (OA). Iron increases are associated with age and gene mutation. In the present study, we examined whether serum ferritin, an indicator of total body iron stores, correlates with clinical features in patients with OA, and whether the hemochromatosis Fe (HFE) gene mutation plays a role. METHODS: In a 2-year longitudinal observational study, 127 patients with knee OA and 20 healthy individuals (controls) were enrolled. All patients underwent standardized weight-bearing fixed-flexion posteroanterior knee radiographs. Peripheral blood samples were analyzed for serum ferritin, and genotyped for HFE using allelic discrimination methods. RESULTS: Higher levels of serum ferritin were found in patients older than 56 years (P =0.0186) and males (P =0.0006), with a trend toward higher ferritin in patients with OA. HFE gene mutation carriers were more prevalent among patients with OA than among healthy controls. When stratified further by gender, we found that male patients with OA had higher levels of serum ferritin than male control subjects [odds ratio = 4.18 (limits of 95% confidence interval: 0.86-27.69, P = 0.048)]. Analyses of radiographic data indicated that higher ferritin was associated with narrower joint space width at baseline (P = 0.032) in male patients. Additionally, among men, risk prediction of radiographic severity [Kellgren-Lawrence (KL) grade >2)] in the higher ferritin group was almost five times that of the lower ferritin group (odds ratio = 4.74, P = 0.023). CONCLUSION: Our data suggest that increased ferritin levels are associated with symptomatic knee OA in males. This finding needs to be validated in a larger cohort of patients.

PURPOSE OF REVIEW: Despite the progress toward understanding the molecular pathogenesis of rheumatoid arthritis (RA), its cause remains elusive. Genes are important but rather insufficient to explain the majority of RA cases. This review describes the novel data supporting the microbiome and its interactions with the human host as potential en('in')vironmental factors in RA pathogenesis. RECENT FINDINGS: Animal models of inflammatory arthritis have shown that the presence of bacteria in mucosal surfaces is sufficient to alter local and systemic host immune responses and elicit joint inflammation. Human RA studies have focused on three mucosal sites: the gut, the gingiva, and the respiratory tree. The oral microbiome, and specifically Porphyromonas gingivalis, has long been implicated. Novel sequencing technologies have allowed investigations into the role of the gut microbiome in the development of autoimmune arthritis. Most recently, the pulmonary parenchyma has also been described as yet another possible mucosal site of initiation of autoimmunity in RA. SUMMARY: Emerging data implicate the microbiome in RA pathogenesis. Mucosal sites exposed to a high load of bacterial antigens - such as the periodontium, lung, and gut - may represent the initial site of autoimmune generation. If validated, these findings could lead to the discovery of potential biomarkers and therapeutic approaches in the preclinical and clinical phases of RA.

Rheumatoid arthritis, currently regarded as a complex multifactorial disease, was initially characterized as such at the turn of the 19th century. Ever since, multiple lines of investigation have attempted to elucidate the etiological factor(s) involved in disease incidence. Genes - including those risk alleles within HLA-DR4 - have been implicated but are insufficient to explain the vast majority of cases. Several environmental factors, therefore, are being studied. Among them, the role of periodontal disease and Porphyromonas gingivalis in the pathogenesis of rheumatoid arthritis has attracted both clinical and bench interest given supportive epidemiologic and mechanistic data.

Rheumatoid arthritis (RA) is a prevalent systemic autoimmune disease, caused by a combination of genetic and environmental factors. Animal models suggest a role for intestinal bacteria in supporting the systemic immune response required for joint inflammation. Here we performed 16S sequencing on 114 stool samples from rheumatoid arthritis patients and controls, and shotgun sequencing on a subset of 44 such samples. We identified the presence of Prevotella copri as strongly correlated with disease in new-onset untreated rheumatoid arthritis (NORA) patients. Increases in Prevotella abundance correlated with a reduction in Bacteroides and a loss of reportedly beneficial microbes in NORA subjects. We also identified unique Prevotella genes that correlated with disease. Further, colonization of mice revealed the ability of P. copri to dominate the intestinal microbiota and resulted in an increased sensitivity to chemically induced colitis. This work identifies a potential role for P. copri in the pathogenesis of RA. DOI: http://dx.doi.org/10.7554/eLife.01202.001.

Purpose:To assess the potential use of sodium magnetic resonance (MR) imaging of cartilage, with and without fluid suppression by using an adiabatic pulse, for classifying subjects with versus subjects without osteoarthritis at 7.0 T.Materials and Methods:The study was approved by the institutional review board and was compliant with HIPAA. The knee cartilage of 19 asymptomatic (control subjects) and 28 symptomatic (osteoarthritis patients) subjects underwent 7.0-T sodium MR imaging with use of two different sequences: one without fluid suppression (radial three-dimensional sequence) and one with fluid suppression (inversion recovery [IR] wideband uniform rate and smooth truncation [WURST]). Fluid suppression was obtained by using IR with an adiabatic inversion pulse (WURST pulse). Mean sodium concentrations and their standard deviations were measured in the patellar, femorotibial medial, and lateral cartilage regions over four consecutive sections for each subject. The minimum, maximum, median, and average means and standard deviations were calculated over all measurements for each subject. The utility of these measures in the detection of osteoarthritis was evaluated by using logistic regression and the area under the receiver operating characteristic curve (AUC). Bonferroni correction was applied to the P values obtained with logistic regression.Results:Measurements from IR WURST were found to be significant predicators of all osteoarthritis (Kellgren-Lawrence score of 1-4) and early osteoarthritis (Kellgren-Lawrence score of 1 or 2). The minimum standard deviation provided the highest AUC (0.83) with the highest accuracy (>78%), sensitivity (>82%), and specificity (>74%) for both all osteoarthritis and early osteoarthritis groups.Conclusion:Quantitative sodium MR imaging at 7.0 T with fluid suppression by using adiabatic IR is a potential biomarker for osteoarthritis.(c) RSNA, 2013.

OBJECTIVE: To assess the relationship between knee alignment and subregional T1rho values of the femorotibial cartilage and menisci in patients with mild (Kellgren-Lawrence grade 1) to moderate (KL3) osteoarthritis (OA) at 3T. MATERIALS AND METHODS: 26 subjects with a clinical diagnosis of KL1-3 OA were included and subdivided into three subgroups: varus, valgus, and neutral. All subjects were evaluated on a 3T MR scanner. Mann-Whitney and Wilcoxon signed rank tests were performed to determine any statistically significant differences in subregional T1rho values of femorotibial cartilage and menisci among the three subgroups of KL1-3 OA patients. RESULTS: Medial femoral anterior cartilage subregion in varus group had significantly higher (p<0.05) T1rho values than all cartilage subregions in valgus group. Medial tibial central cartilage subregion had significantly higher T1rho values (p<0.05) than lateral tibial central cartilage subregion in varus group. The posterior horn of the medial meniscus in neutral group had significantly higher T1rho values (p<0.0029) than all meniscus subregions in valgus group. CONCLUSION: There exists some degree of association between knee alignment and subregional T1rho values of femorotibial cartilage and menisci in patients with clinical OA.