Neurological autoantibody prevalence in chronic epilepsy: Clinical and neuropathologic findings.

BACKGROUND: We aimed to explore the prevalence of autoimmune antibodies (Abs) in a large consecutive series with "chronic" epilepsy and without symptoms of autoimmune encephalitis; and to compare the immunopathology of brain tissue from drug-resistant epilepsy (DRE) with and without Abs positivity. METHODS: Neuronal and glial antibodies were detected in the serum of patients who were admitted to the wards of West China Hospital from October 2016 to September 2019 and had epilepsy by cell-based assays and tissue-based assays. RESULTS: Twenty-one (6.8 %) of 328 patients had positive Ab findings for the following: dipeptidyl-peptidase-like protein-6 (n = 7), contactin-associated protein-like 2 (n = 5), glutamic acid decarboxylase 65 (n = 4), gamma aminobutyric acid beta receptor (n = 2), N-methyl-d-aspartate receptor (n = 2), and dopamine D2 receptor (n = 1). Antibodies were detected in 6.9 % (13/187) of epilepsy people with unknown etiology and 5.6 % (8/141) of patients with known etiology, respectively. Among 190 patients with DRE, 14 (7.3 %) patients were Abs-positive. There was no significant difference between individuals with seropositive and seronegative results in clinical manifestations, except that the history of febrile seizure was significantly more frequent in the seropositive group. Moreover, brain samples from 3 patients with Abs-positive DRE (with DPPX in 2 patients, and CASPR2 in 1 patient) and 18 patients with Abs-negative DRE were analyzed for immunopathology. We found higher expression of CD8-positive T-cells in the hippocampus of Abs-positive DRE group. CONCLUSIONS: Neuronal antibodies are potentially involved in the process of "chronic" epilepsy, and CD8-positive T-cells may play an important role in this process.

Acupuncture for aqueous deficiency dry eye: a randomized controlled trial. / é’ˆåˆºæ²»ç–—æ°´æ¶²ç¼ºä¹åž‹å¹²çœ¼ï¼šéšæœºå¯¹ç §è¯•éªŒ.

OBJECTIVES: To compare the clinical efficacy and safety of acupuncture and sodium hyaluronate eye drop in the treatment of aqueous deficiency dry eye. METHODS: A total of 60 patients (120 eyes) with aqueous deficiency dry eye were randomly divided into an observation group (30 cases, 1 case dropped out) and a control group (30 cases, 1 case dropped out). In the control group, sodium hyaluronate eye drop were used, one drop at a time, 4 times a day, for 14 consecutive days. In the observation group, acupuncture was applied at bilateral Shangjingming (Extra), Cuanzhu (BL 2), Sizhukong (TE 23), Taiyang (EX-HN 5), and Tongziliao (GB 1) , once a day, treatment for 6 days with the interval of 1 day was required, for 14 consecutive days. The tear meniscus height (TMH), Schirmer Ⅰ test (SⅠT), ocular surface disease index (OSDI) score, non-invasive tear break-up time (NIBUT), and corneal fluorescein sodium staining (FLS) score were compared between the two groups before and after treatment, and the safety of the treatment of the two groups was observed. RESULTS: Compared with those before treatment, after treatment, TMH, SⅠT and NIBUT were increased (P<0.01, P<0.05), and FLS scores were decreased (P<0.01) in the two groups; the score of OSDI was reduced (P<0.01) in the observation group. After treatment, in the observation group, TMH and SⅠT were higher than those in the control group (P<0.01), and the score of OSDI was lower than that in the control group (P<0.01). No adverse reactions and adverse events were observed in the two groups. CONCLUSIONS: Acupuncture and sodium hyaluronate eye drop can both effectively treat aqueous deficiency dry eye, acupuncture has obvious advantages in improving TMH and basic tear secretion, and reducing the subjective symptoms of patients. Acupuncture for dry eye is safe.

Nickel-Catalyzed Reductive Cross-Coupling of Aziridines and Allylic Chlorides.

A nickel-catalyzed reductive cross-coupling of aziridines and allylic chlorides was realized by using manganese metal as the reducing agent. This protocol afforded a convenient approach to obtain ß-allyl-substituted arylethylamines bearing various functional groups. The utility of this reaction was also demonstrated by scale-up preparation and diverse transformations, including the synthesis of Baclofen and several bioactive molecular motifs.

Nickel-Catalyzed Reductive Three-Component Cross-Coupling of Butadiene with Aldehydes and Alkenyl Triflates/Bromides: Access to Skipped Dienes.

A regio- and stereoselective nickel-catalyzed reductive three-component cross-coupling of 1,3-butadiene with aldehydes and alkenyl triflates or bromides was realized. This protocol afforded a convenient approach to the synthesis of skipped diene compounds bearing various functionals and heterocyclic groups. The utility of this reaction was also demonstrated by scale-up preparation and diverse transformations.

Response to Surgery Assessments for Sparing Radioiodine Remnant Ablation in Intermediate-Risk Papillary Thyroid Cancer.

CONTEXT: Using response to surgery when tailoring radioiodine (RAI) therapy for papillary thyroid cancer (PTC) is valued but lacks prospective validation. OBJECTIVE: To spare RAI thyroid remnant ablation among patients with intermediate-risk PTCs using 3-tiered assessments with response to surgery highlighted, in addition to the risk of the recurrence stratification and TNM staging. METHODS: Patients with no evidence of disease (NED) identified as excellent response (ER) or indeterminate response (IDR) to surgery were spared from RAI thyroid remnant ablation after informed consent and prospectively enrolled under active surveillance. Those involved in other trials or without sufficient follow-up data were excluded. Dynamic responses were followed and compared longitudinally. The main outcome measures were NED presenting as durable ER or IDR for over 12 months. RESULTS: Of the enrolled 215 patients, 47.4% (102/215) ER and 52.6% (113/215) IDR were identified regarding RAI decision-making. After a median of 23.6 (interquartile range 13.8-31.6) months, the share of ER increased to 82.8% (178/215) and IDR decreased to 16.3% (35/215), with 85 patients shifting from IDR to ER over time, only 0.5% (1/215) structural incomplete response and 0.5% (1/215) biochemical incomplete response observed. Successful remnant ablation was observed in 27.7% (26/94) of the patients completing 2 diagnostic whole-body scans after a median interval of 13.0 months, indicating a theranostic effect. In the 173 patients followed for over 12 months, the NED rate did not differ between ER and IDR subgroups (100% vs 97.9%, P = .20). CONCLUSION: Through the 3-tiered assessments with response to surgery highlighted, postoperative ER and IDR spared from RAI remnant ablation may indicate similar favorable responses in intermediate-risk patients with PTC during 23.6 months of follow-up.

The detection of up-regulated anti-thyroid antibodies and autoimmune thyroid diseases in patients with autoimmune encephalitis: a retrospective study of 221 patients.

OBJECTIVE: To investigate the potential detection rate of anti-thyroid antibodies' (ATAbs) positivity, thyroid dysfunctions, and autoimmune thyroid diseases (AITDs) in autoimmune encephalitis (AE) and to analyze whether thyroid autoimmunity/dysfunction can affect the clinical course of AE. METHODS: Two hundred twenty-one AE patients and 229 age- and sex-matched controls were included in this study. We measured the levels of ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) and thyroid hormones in all the individuals. In addition, the association of thyroid autoimmunity/dysfunctions with functional outcomes of AE was identified by using logistic regression and Kaplan-Meier analyses. RESULTS: The prevalence of TPOAb-positive and TgAb-positive was significantly higher in AE patients (16.3% and 16.7%, respectively) as compared with controls (9.6% and 7.4%, respectively; P = 0.034 and P = 0.002, respectively). In addition, the free triiodothyronine (fT3) level was significantly lower in AE patients as compared to the controls (P < 0.001). However, the frequency of AITDs (Hashimoto's thyroiditis and Graves' disease) did not significantly differ between AE patients and control subjects. Importantly, low fT3 was found to be associated with poor functional outcomes at the 3-month follow-up in AE. Adjustment of potential confounders did not change the association. However, the presence of ATAbs did not significantly alert the disease course of AE. CONCLUSIONS: ATAbs-positive and/or AITD patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

Assessment of acute kidney injury risk using a machine-learning guided generalized structural equation model: a cohort study.

BACKGROUND: Acute kidney injury is common in the surgical intensive care unit (ICU). It is associated with poor patient outcomes and high healthcare resource usage. This study's primary objective is to help identify which ICU patients are at high risk for acute kidney injury. Its secondary objective is to examine the effect of acute kidney injury on a patient's prognosis during and after the ICU admission. METHODS: A retrospective cohort of patients admitted to a Singaporean surgical ICU between 2015 to 2017 was collated. Patients undergoing chronic dialysis were excluded. The outcomes were occurrence of ICU acute kidney injury, hospital mortality and one-year mortality. Predictors were identified using decision tree algorithms. Confirmatory analysis was performed using a generalized structural equation model. RESULTS: A total of 201/940 (21.4%) patients suffered acute kidney injury in the ICU. Low ICU haemoglobin levels, low ICU bicarbonate levels, ICU sepsis, low pre-ICU estimated glomerular filtration rate (eGFR) and congestive heart failure was associated with the occurrence of ICU acute kidney injury. Acute kidney injury, together with old age (> 70 years), and low pre-ICU eGFR, was associated with hospital mortality, and one-year mortality. ICU haemoglobin level was discretized into 3 risk categories for acute kidney injury: high risk (haemoglobin ≤9.7 g/dL), moderate risk (haemoglobin between 9.8-12 g/dL), and low risk (haemoglobin > 12 g/dL). CONCLUSION: The occurrence of acute kidney injury is common in the surgical ICU. It is associated with a higher risk for hospital and one-year mortality. These results, in particular the identified haemoglobin thresholds, are relevant for stratifying a patient's acute kidney injury risk.

Adherence to the Dietary Approaches to Stop Hypertension Diet and Hyperuricemia: A Cross-Sectional Study.

OBJECTIVE: Although several individual nutrients/foods are associated with uric acid status, the association of overall diet quality with hyperuricemia remains unclear. The current study was undertaken to examine the association between adherence to the Dietary Approaches to Stop Hypertension (DASH) diet and the odds of having hyperuricemia in a Chinese adult population. METHODS: Included were 71,893 Chinese participants in the Kailuan I study and the Kailuan II study (mean age 51.4 years) who were free of gout prior to or in 2014. Dietary intakes were assessed using a validated food frequency questionnaire, and the DASH diet score was calculated based on consumptions of vegetables, fruit, dairy, beans, whole grains, meat, fat, sodium, and sugar-sweetened beverages. Fasting blood samples were collected in 2014, and hyperuricemia was defined as serum uric acid concentrations of ≥7 mg/dl for men, and of ≥6 mg/dl for women. The association between DASH diet score and hyperuricemia was assessed using multiple logistic regression models, adjusting for age, sex, total energy, obesity, physical activity, education, smoking, alcohol drinking, blood pressure, fasting glucose, lipid profiles, renal function, and presence of cardiovascular disease. RESULTS: A High DASH diet score was associated with low odds of having hyperuricemia (adjusted odds ratio for quartile 4 versus quartile 1 0.70 [95% confidence interval 0.66, 0.75], P for trend < 0.001) after adjusting for potential confounders. The association between the DASH diet and hyperuricemia was more pronounced among older individuals (age ≥50 years), women, and physically inactive participants compared with their counterparts (P for interaction < 0.01 for all). CONCLUSION: The DASH diet was associated with a low likelihood of having hyperuricemia in Chinese adults.

[Significance of Dynamic Risk Assessment in the Follow-up of Non-distant Metastatic Differentiated Thyroid Cancer Patients with Intermediate and High Risk].

Objective To tailor the subsequent treatment and follow-up strategy,this study dynamically assessed the response to initial therapy in non-distant metastatic differentiated thyroid cancer (DTC) patients with intermediate and high risk. Methods A total of 184 non-distant metastatic DTC patients (intermediate-risk 111 cases and high-risk 73 cases) were retrospectively enrolled in this study. Based on the results of initial response assessment (6-12 months after initial therapy),patients were divided into two groups:excellent response (ER) group (n=113) and non-excellent response (non-ER) group (n=71). We compared the differences in clinicopathological features between these 2 groups and evaluated the changes of dynamic response to therapy at the initial and final assessments after initial therapy in all patients. Results Compared with the ER group,the non-ER group showed a larger tumor size (U=2771.500,P=0.000),higher proportion of extrathyroidal invasion (χ 2=4.070,P=0.044),and higher preablative-stimulated thyroglobulin levels (U=1367.500,P=0.000). ER was achieved in 31% of patients in the initial non-ER group [including indeterminate response (IDR) and biochemical incomplete response (BIR)] at the final follow-up only by thyroid stimulating hormone (TSH) suppression therapy,among which 63.6% were with intermediate risk (especially the patients with IDR) and 36.4% at high risk. In addition,5.2%(6/113) of patients in the initial ER group were reassessed as IDR,BIR,or even structural incomplete response at the end of the follow-up (among which one patient developed into cervical lymph node recurrence,as confirmed by pathology);the TSH level in these patients fluctuated at 0.56-10.35 µIU/ml and was not corrected in time during the follow-up after initial therapy. Conclusions Some of non-distant metastatic DTC patients with intermediate and high risks who presented initial non-ER may achieve ER only by TSH suppression therapy over time;in contrast,the patients presented initial ER may develop into non-ER without normalized TSH suppression therapy. The dynamic risk assessment system may provide a real-time assessment of recurrence risk and tailor the subsequent treatment and follow-up strategies.

UNFAVORABLE RESPONSES TO RADIOIODINE THERAPY IN N1B PAPILLARY THYROID CANCER: A PROPENSITY SCORE MATCHING STUDY.

Objective: Regional nodal metastases carry prognostic significance in papillary thyroid cancer (PTC). However, whether different locational nodal metastases correlate with different therapeutic responses remains controversial. We innovatively applied the response to therapy restratification system to evaluate the dynamic disease status after surgery and radioactive iodine (RAI) therapy in PTC patients with different locational nodal metastases. Methods: A total of 585 nondistant-metastatic PTC patients who underwent total thyroidectomy and RAI therapy were retrospectively enrolled. Patients with nodal metastases were categorized into N1a and N1b groups. Propensity score matching was used to balance the bias between the 2 groups. Therapeutic responses were dynamically evaluated, and responses to RAI therapy were classified into excellent (ER), indeterminate (IDR), biochemical incomplete (BIR) and structural incomplete response (SIR). Results: N1b group patients showed a significantly higher pre-ablation stimulated thyroglobulin (Ps-Tg) level than N1a group patients (7.4 ng/mL versus 3.2ng/mL, P<.001). After RAI therapy, N1b group patients took a longer time to achieve ER (9.86 months versus 3.29 months, P<.001) and exhibited a higher proportion of non-ER (IDR, BIR, and SIR) (39.15% versus 17.46%, P<.001) compared to N1a group patients. In logistic regression, N1b and Ps-Tg ≥10 ng/mL were confirmed to be independent factors predicting non-ER (odds ratio: 2.591, and 9.196, respectively). In Cox regression, patients with N1b disease and Ps-Tg ≥10 ng/mL showed significantly lower hazards for achieving ER (hazard ratio: 0.564, and 0.223, respectively). Conclusion: N1b PTC patients showed inferior responses to surgery and RAI therapy compared to N1a patients. N1b was confirmed to be an independent factor predicting unfavorable responses to RAI therapy. Abbreviations: AJCC = American Joint Committee on Cancer; ATA = American Thyroid Association; BIR = biochemical incomplete response; BRAFV600E = proto-oncogene B-Raf V600E mutation; CI = confidence interval; CT = computed tomography; DNA = deoxyribonucleic acid; DTC = differentiated thyroid cancer; ER = excellent response; ETE = extrathyroidal extension; HR = hazard ratio; IDR = indeterminate response; LNM = lymph node metastasis; N1a = central cervical LNM; N1b = lateral cervical LNM; OR = odds ratio; PSM = propensity score matching; Ps-Tg = pre-ablation stimulated thyroglobulin; PTC = papillary thyroid cancer; RAI = radioactive iodine; SIR = structural incomplete response; Tg = thyroglobulin; TgAb = thyroglobulin antibody; TSH = thyroid-stimulating hormone.

Bacterial community shaped by heavy metals and contributing to health risks in cornfields.

Scientists are increasingly aware that heavy metal contamination in soils, especially in farmland ecosystems, can negatively affect human health and alter the bacterial community that plays a critical role in plant growth and heavy metal accumulation. The goal of the present paper was to uncover how various heavy metals and non-metallic elements affect human health and bacterial diversity in cornfields and to explore the contribution of soil bacteria to heavy metal accumulation in crops. Soil samples were collected from five counties in Shandong Province, China, where abnormally high levels of heavy metals and metalloids were caused by mining and heavy industry. We calculated a hazard quotient (HQ) to evaluate the health risk these heavy metals cause and analyzed the soil bacterial community using 16S rRNA gene sequencing. The HQ results showed that As posed the greatest threat to human health followed by Pb although concentrations of all metals did not reach the health risk threshold. Meanwhile, principal component analysis (PCA) and redundancy analysis (RDA) revealed soil bacterial richness was significantly influenced by As, Ni, and Cr as well as pH and phosphorus, but not by the species diversity of aboveground weeds. The most abundant bacteria in our study region were heavy metal tolerant groups, specifically Actinobacteria and Proteobacteria. Moreover, correlation analysis suggested that Actinobacteria might reduce the phytoaccumulation of Cr, Cu, Zn, and Hg in corn, while Proteobacteria might weaken phytoaccumulation of Pb, Ni, As, and Cd. Our results verified that heavy metals play an important role in shaping the soil bacterial community. Using native bacteria in farmland provides a potential biological strategy for reducing the health risk posed by heavy metals related to food consumption.

Spatial trends and pollution assessment for mercury in the surface soils of the Nansi Lake catchment, China.

Surface soil samples collected from Nansi Lake catchment were analyzed for mercury (Hg) to determine its spatial trends and environmental impacts. Results showed that the average soil Hg contents were 0.043 mg kg-1. A positive correlation was shown between TOC and soil Hg contents. The main type of soil with higher TOC contents and lower pH values showed higher soil Hg contents. Soil TOC contents and CV values were both higher in the eastern catchment. The eastern part of the catchment, where the industry is developed, had relatively high soil Hg contents and a banding distribution of high Hg contents was corresponded with the southwest-northeast economic belt. Urban soils had higher Hg contents than rural soils. The urbanization pattern that soil Hg contents presented a decreasing trend from city center to suburb was shown clearly especially in the three cities. Soil Hg contents in Jining City showed a good consistency with the urban land expansion. The spatial trends of soil Hg contents in the catchment indicated that the type and the intensity of human activities have a strong influence on the distribution of Hg in soils. Calculated risk indices showed that the western part of the catchment presented moderately polluted condition and the eastern part of the catchment showed moderate to strong pollution level. The area with high ecological risk appeared mainly along the economic belt.

Association of serum uric acid and risk of hypertension in adults: a prospective study of Kailuan Corporation cohort.

Whether hyperuricemia is an independent risk factor for hypertension in adults is still under debate. To determine the association between serum uric acid and risk of hypertension in the Chinese population, we conducted a prospective study using the "Kailuan Corporation cohort." A total of 39,233 adult subjects with available data on serum uric acid were enrolled from 2006 to 2007. Subjects with established hypertension were excluded and were then grouped based on the gender and baseline quartile serum uric acid into F1-4 for women and M1-4 for men with F1 and M1 being the lowest quartiles. Incidence of newly described primary hypertension was reevaluated in 2010-2011. The median (interquantile range) baseline uric acid (UA) was 290 (243-344) µmol/L in men and 230 (194-274) µmol/L in women. During a 4-year follow-up period, 12,844 subjects (31.31 %) were newly diagnosed with hypertension. The incidence of hypertension was 14.36, 16.57, 19.06, and 22.35 % in F1 to F4 and 33.64, 33.97, 36.54, and 40.74 % in M1 to M4, respectively. Multiple logistic regression analysis showed that the odds ratios (ORs) of incident hypertension were 1.17 [95 % confidence interval (CI) 1.00-1.37, P = 0.055], 1.24 (95 % CI 1.06-1.45, P = 0.009), and 1.20 (95 % CI 1.02-1.41, P = 0.027) in F2 to F4 compared to the F1 and 0.98 (95 % CI 0.91-1.05, P = 0.534), 1.05 (95 % CI 0.98-1.13, P = 0.190), and 1.13 (95 % CI 1.05-1.22, P = 0.002) in M2 to M4 compared to the M1. Elevated level of serum uric acid is associated with an increased risk of hypertension in adults.

[Anatomy of temporomandibular joint and condyle position in Uygur adult patients evaluated with cone-beam CT].

PURPOSE: To compare the anatomy and condyle-fossa relationship difference between Uygur adult patients with Class I and Class II division 1 malocclusion by three dimensional cone-beam CT (CBCT). METHODS: Sixty-four patients with Class I and Class II division 1 malocclusion were selected, and the CBCT scans of their temporomandibular joints were taken.The difference of the condylar morphology and location between Class I and Class II division 1 patients was analyzed with SPSS 17.0 software package. RESULTS: The position of condyle in the TMJ fossa was not significantly different between the two groups; in Class II division 1 malocclusion group, the mandibular fossa depth, anterior joint space and the superior joint space were significantly bigger (P<0.05), but the posterior joint space was significantly smaller than those in Class I malocclusion group (P<0.05). CONCLUSIONS: There were difference in condyle position and TMJ morphology between Class I and Class II division 1 malocclusion group in Uygur adult patients.

[Residues and Spatial Distribution Characteristics of Organochlorine Pesticides DDTs in Soil of Linyi City, Shandong Province].

Surface soil samples were collected every 36 km2 from Linyi City to study the residues, composition and origin, influencing factors, spatial distribution and environment quality characteristics of soil DDTs. Measurements were taken for DDTs, OrgC, N, etc. for all samples. The results indicated that the detectable rate of DDTs was 71. 75%, and the mean content of DDTs was 0. 035 µg.g-1. p,p'-DDT and p,p'-DDE were the predominant contaminant compounds, with mean concentrations of 0.033 µg.g-1 and 0.010 µg.g-1, and accounted for 60. 99% and 34. 62% of the detectable samples, respectively. The degradation rate of DDTs suggested that 58% surface soils were recently inputted, these newly inputted locations were especially distributed in the middle to south of the study area, meanwhile, p,p'-DDD/p,p'-DDE revealed that the degradation of DDTs was mainly under oxidizing condition, and o,p'-DDT/p,p'-DDT illustrated that 71. 37% DDTs in soils of the study area were concerned with technical DDTs sources. Besides, the correlation, analysis showed that the external factors affecting the distribution of DDTs included OrgC, N, C and pH etc. and the higher the p, p'-DDT proportion of DDTs, the greater the effect. The distribution of DDTs had an obvious point source characteristic, and significant concentration centers were located nearby the cities and counties, typically, the DDTs concentrations of middle to southern area were much higher. However, DDTs environmental quality assessment suggested that the pollution level was relatively low, and the soil was mainly classified into grade I or II, which accounted for 78. 95% and 21. 05% of the whole study area, respectively.

Incomplete B cell tolerance to cartilage oligomeric matrix protein in mice.

OBJECTIVE: Cartilage oligomeric matrix protein (COMP) is a major noncollagenous component of cartilage and is used as a biomarker in rheumatoid arthritis and experimental arthritis. Injection of COMP leads to severe inflammatory joint disease, and antibodies play a critical role in mediating arthritis. The arthritogenicity of COMP might be due to the lack of self tolerance. This study was undertaken to determine the status of COMP-specific B cell tolerance using COMP-deficient mice. METHODS: Arthritis development and antibody responses were compared between COMP-sufficient and COMP-deficient littermates after immunization with rat COMP. Serum anti-COMP antibody levels were measured using a panel of recombinant mouse COMP proteins, and antibody-secreting cells were enumerated by enzyme-linked immunospot assays. A novel sandwich enzyme-linked immunosorbent assay was developed to assess COMP molecules in serum. RESULTS: COMP-sufficient mice, but not COMP-deficient mice, developed severe arthritis following immunization with rat COMP. However, anti-COMP antibody titers to native COMP and recombinant protein domains covering the entire mouse COMP sequence, except the less immunodominant type 3 repeat domains, were decreased in COMP-sufficient mice compared to COMP-deficient mice. In addition, COMP-sufficient mice had fewer B cells secreting COMP-reactive antibodies. Detectable levels of full-length COMP in arthritic COMP-sufficient B10.Q NCF-1(*/*) and healthy mice suggested systemic availability of COMP to the immune system. CONCLUSION: The lack of arthritis, together with high levels of COMP-specific antibodies, in COMP-deficient mice indicates that susceptibility to arthritis is COMP specific and that endogenous expression of COMP in wild-type mice tolerizes B cells in vivo.