Chondroitin sulphation patterns in synovial fluid in osteoarthritis subsets

OBJECTIVES: To determine concentrations of chondroitin sulphate (CS) disaccharides in knee synovial fluid (SF) from normal subjects and patients with osteoarthritis (OA) or rheumatoid arthritis (RA), to test whether these variables differ between different diseases and subsets of OA. METHODS: OA was subdivided into large joint OA (LJOA), nodal generalised OA (NGOA), and OA with calcium pyrophosphate crystal deposition (CPA), with 25, 9, and 11 people in each subset respectively. The SF of 13 normal subjects was also volunteered for analysis along with 15 RA patients. Clinical assessment of inflammation (0-6) was undertaken on OA and RA knees. Concentrations of unsaturated CS disaccharides Deltadi6S and Deltadi4S were measured by capillary zone electrophoresis. RESULTS: Concentrations of Deltadi6S were lower in RA (5.90 ng/ml) and OA (13.24 ng/ml) fluids compared with normal (21.0 ng/ml) but no significant differences were seen between disease and normal fluids for Deltadi4S (about 4-6 ng/ml). The ratio of Deltadi6S:Deltadi4S were RA相似文献   

Chondroitin and keratan sulphate epitopes, glycosaminoglycans, and hyaluronan in progressive versus non-progressive osteoarthritis

OBJECTIVE—To determine if a single time point estimation of chondroitin sulphate (CS) or keratan sulphate (KS) epitopes, hyaluronan (HA), or total glycosaminoglycans (GAG) in knee synovial fluid at time of hospital referral can predict subsequent radiographic progression of knee osteoarthritis.
METHODS—Two groups of hospital referred patients with knee osteoarthritis were compared: (1) a "progressive" group (n = 45), showing further reduction in radiographic joint space of at least one grade (0-3) in at least one compartment; and (2) a "non-progressive" group (n = 25) in whom radiographs showed no change during the mean follow up period of 2.3 years (median 2, range 1 to 5 years). Knee synovial fluid obtained at the first visit was examined by ELISA for: CS epitopes, using monoclonal antibodies 3B3 and 7D4; KS epitope, using monoclonal antibody 5D4; and HA, using biotinylated HA binding region of cartilage proteoglycan. Total sulphated GAG were measured by dye binding with 1:9 dimethylmethylene blue.
RESULTS—In patients with bilateral synovial fluid data right and left knee values were closely correlated for all variables. There were no significant differences between CS and KS epitopes, HA, total sulphated GAG, or ratios of individual CS or KS epitopes to total GAG, between progressive and non-progressive groups.
CONCLUSIONS—Single time point estimation of CS, KS, HA, or total GAG in synovial fluid does not distinguish radiographically progressive and non-progressive knee osteoarthritis patients followed for two years.

     

Changes in glycosaminoglycan epitope levels in knee joint fluid following injury

Objective. To measure the levels of epitopes on the chondroitin sulfate (CS) and keratan sulfate (KS) chains of proteoglycan fragments in synovial fluids from injured and contralateral uninjured knees of patients with traumatic cruciate ligament and/or meniscus damage. Methods. Enzyme-linked immunosorbent assays were used to determine the levels of monoclonal antibody epitopes 3-B-3 and 7-D-4 (CS), and 5-D-4 (KS), in paired joint fluids from the injured and uninjured knees of trauma patients. Results. Levels of the CS epitopes were increased in the trauma joint fluids from most patients, with higher levels of 3-B-3 epitope in 12 of the 16 patients, but the difference did not achieve significance; however, 7-D-4 levels were higher in 15 patients, and the difference was highly significant (P = 0.0005). In contrast, the KS epitope detected by 5-D-4 was decreased in 13 of 15 patients, and the difference was significant (P = 0.0074). Conclusion. The increased level of 7-D-4 epitope on proteoglycans in joint fluid from injured knees may reflect the response of the articular cartilage to acute trauma resulting in altered expression of specific CS epitopes on cartilage proteoglycans. The fall in KS epitope levels may reflect the synthesis of proteoglycans that have lower KS content.     

Relations between synovial fluid and serum concentrations of osteocalcin and other markers of joint tissue turnover in the knee joint compared with peripheral blood

OBJECTIVE—To determine if osteocalcin (OC) is locally produced in the joint and to study the relation between markers of bone, cartilage, and synovial tissue turnover.
METHODS—The concentrations of OC, keratan sulphate epitope (5D4), and hyaluronate (HA) were measured in paired serum and synovial fluid in 10 healthy volunteers and 15 patients with osteoarthritis (OA) and 16 with rheumatoid arthritis (RA). OC was measured with a commercial immunoradiometric assay and concentrations of 5D4 and HA were measured using enzyme linked immunosorbent inhibition assays.
RESULTS—Synovial fluid OC was found to be significantly lower than serum (p< 0.001) in all patients and controls. Synovial fluid OC concentrations were directly correlated with serum concentrations (r=0.63, p<0.001) and with age (r = 0.48, p< 0.01). There were also some relations between OC, HA, and 5D4 in patients with OA and RA. The OC concentrations were directly correlated with HA (r=0.68, p<0.01) in OA serum and there was a similar correlation in RA synovial fluid (r=0.69, p<0.01). A weak negative correlation was found between OC and 5D4 in OA serum (r=−0.55, p=0.035) while a weak positive correlation was found in RA serum (r=0.53, p=0.034).
CONCLUSIONS—These results show that more OC is present in the circulation than in knee joint fluids suggesting that synovial fluid OC may be derived from the blood.

     

Detection of oncostatin M in synovial fluid from patients with rheumatoid arthritis

OBJECTIVE—To measure oncostatin M (OSM) in synovial fluid from patients with rheumatoid arthritis (RA) and osteoarthritis (OA).
METHODS—20 samples of synovial fluid from patients with RA and 10 samples from patients with OA were examined using an OSM specific sandwich ELISA.
RESULTS—OSM was detected at concentrations ranging from 2.36 to 901.82 pg/ml in 18 (90%) of 20 samples of synovial fluid from RA patients. There was no detectable OSM in synovial fluid from OA patients. In the RA patients, the OSM concentration in synovial fluid correlated significantly with the synovial fluid white blood cell count (r=0.67, p<0.01), but not with other laboratory parameters of disease activity.
CONCLUSION—These findings suggest that OSM may contribute to joint inflammation in RA.

     

Changes in serum chondroitin sulphate epitopes 3-B-3 and 7-D-4 in early rheumatoid arthritis.

OBJECTIVES: The aims of the present rheumatoid arthritis (RA) study were (1) to examine the levels of serum 3-B-3 and 7-D-4 to find out whether they are different from controls, (2) to find out whether the concentrations of these epitopes change with disease duration in early RA and (3) whether the serum concentrations of 3-B-3 and 7-D-4 in early RA are prognostic for subsequent disease progression. METHODS: The concentrations of 3-B-3 and 7-D-4 in sera were quantitated by immunoassays. RESULTS: The levels of 3-B-3 and 7-D-4 were significantly lower in RA than in controls (3- to 30-fold, P < 0.001). Changes in 3-B-3 and 7-D-4 were apparent with disease duration. At first presentation, the 3-B-3 concentration was lowest and increased at 12 months (3-fold, P < 0.001). This increase was transient since by 24 and 36 months the concentrations were not different to those at first presentation. The level of 7-D-4 was also lowest when the patients first presented at clinic and increased with time at 6 months (2-fold, P < 0.001). The increase was more prolonged for 7-D-4, remaining elevated at 12, 24 and 36 months. The lack of correlations of serum 3-B-3 and 7-D-4 with clinical measurements showed that these markers were not prognostic for disease severity. CONCLUSIONS: The levels of 3-B-3 and 7-D-4 differed between RA and control sera, and changed with disease duration. These markers were not prognostic in predicting disease outcome.     

THE RELEVANCE OF CHONDROITIN AND KERATAN SULPHATE MARKERS IN NORMAL AND ARTHRITIC SYNOVIAL FLUID

This study investigated the synovial fluid concentrations ofglycosaminoglycan (GAG), keratan sulphate (KS) epitope 5D4 andchondroitin sulphate (CS) sulphation patterns in healthy volunteersand patients with osteoarthritis (OA) and rheumatoid arthritis(RA). Synovial fluids were collected from knee joints of healthyvolunteers (n = 24), and patients with OA (n = 28) and RA (n= 29). Concentrations of GAG and the keratan sulphate epitopeSEW were measured in 15 of the healthy volunteers, and all ofthe OA and RA synovial fluids. Total GAG was measured usinga dye-binding method and 5D4 by an ELISA. The unsaturated CSdisaccharides     

Decrease in peripheral type 1 over type 2 T cell cytokine production in patients with rheumatoid arthritis correlates with an increase in severity of disease

Objectives—To compare peripheral type 1 (T1) and type 2 (T2) T cell activities in rheumatoid arthritis (RA) patients with that found for osteoarthritic (OA) patients and healthy controls and to correlate peripheral T1/T2 cell activity in RA with parameters of the disease.
METHODS—Peripheral blood mononuclear cells were isolated from patients with RA (n=66), OA (n=19), and healthy controls (n=15). Primary T cell activity in these mononuclear cells was enhanced by means of anti-CD3/anti-CD28, which mimicks stimulation of T cells by activation of the T cell receptor and a major co-stimulatory signal. Interferon gamma (IFNγ) production and interleukin 4 (IL4) production in the three groups were quantified as measures of T1 and T2 cell activity, respectively, and compared. Serum tumour necrosis factor α (TNFα), erythrocyte sedimentation rate (ESR), C reactive protein (CRP), and joint destruction assessed radiographically of RA patients were determined as parameters of disease activity and correlated with T1/T2 cell activity.
RESULTS—Peripheral T cells from RA patients produced significantly less IFNγ and more IL4 than T cells from both age and sex matched OA patients and healthy controls. Moreover, in RA patients both a decrease in IFNγ and an increase in IL4 production correlated with an increase in serum TNFα, ESR, CRP, and joint destruction.
Conclusions—These results suggest a role for differential T cell activity in RA. In view of the intra-articular T1 cell predominance the results might be explained by selective T1 cell migration into the joint or peripheral suppression of T1 cell activity.

     

Plasminogen activation in synovial tissues: differences between normal, osteoarthritis, and rheumatoid arthritis joints

OBJECTIVE—To analyse the functional activity of the plasminogen activators urokinase (uPA) and tissue type plasminogen activator (tPA) in human synovial membrane, and to compare the pattern of expression between normal, osteoarthritic, and rheumatoid synovium. The molecular mechanisms underlying differences in PA activities between normal and pathological synovial tissues have been further examined.
METHODS—Synovial membranes from seven normal (N) subjects, 14 osteoarthritis (OA), and 10 rheumatoid arthritis (RA) patients were analysed for plasminogen activator activity by conventional zymography and in situ zymography on tissue sections. The tissue distribution of uPA, tPA, uPA receptor (uPAR), and plasminogen activator inhibitor type-1 (PAI-1) was studied by immunohistochemistry. uPA, tPA, uPAR, and PAI-1 mRNA values and mRNA distribution were assessed by northern blot and in situ hybridisations respectively.
RESULTS—All normal and most OA synovial tissues expressed predominantly tPA catalysed proteolytic activity mainly associated to the synovial vasculature. In some OA, tPA activity was expressed together with variable amounts of uPA mediated activity. By contrast, most RA synovial tissues exhibited considerably increased uPA activity over the proliferative lining areas, while tPA activity was reduced when compared with N and OA synovial tissues. This increase in uPA activity was associated with increased levels of uPA antigen and its corresponding mRNA, which were localised over the synovial proliferative lining areas. In addition, in RA tissues, expression of the specific uPA receptor (uPAR) and of the plasminogen activator inhibitor-type 1 (PAI-1) were also increased.
CONCLUSION—Taken together, these results show an alteration of the PA/plasmin system in RA synovial tissues, resulting in increased uPA catalytic activity that may play a part in tissue destruction in RA.

     

Matrix metalloproteinase activity in equine synovial fluid: influence of age, osteoarthritis, and osteochondrosis

OBJECTIVE—To investigate the influence of age, osteoarthritis (OA), and osteochondrosis (OC) on the matrix metalloproteinase (MMP) activity in the synovial fluid (SF) of equine joints.
METHODS—SF was collected from normal and osteoarthritic metacarpophalangeal joints (normal: 14 adult, 28 juvenile; OA: 22 adult). And from normal and osteochondrotic tarsocrural joints (5 months: 11 normal, 8 OC; 11 months: 7 normal, 6 OC). Subsequently, overall MMP activity was measured.
RESULTS—The level of active MMPs was almost twofold higher in SF from juvenile horses (age up to 11 months) than in SF from mature animals (4-30 years; p<0.001). In juvenile horses MMP activity was higher in 5 month old foals than in 11 month old foals (p<0.01). In adult horses MMP activity was independent of age. In OA joints the activity was nearly twice as high as in normal joints (p<0.001). In OC joints MMP activity was not significantly different from normal, age matched, control joints.
CONCLUSIONS—MMP activity in SF from normal adult joints is not related to age. In juvenile joints MMP activity is significantly higher than activity in joints from adult animals. It is hypothesised that the gradual decrease in MMP activity with increasing age reflects the declining metabolic activity resulting from ceasing growth and the accompanying decrease in cartilage remodelling. The increased MMP activity in osteoarthritic joints most likely reflects matrix destruction. In osteochondrosis MMP mediated matrix degradation appears not to be different from normal joints.

Keywords: horse; synovial fluid; matrix metalloproteinases; age     

IS OSTEOARTHRITIS IN WOMEN AFFECTED BY HORMONAL CHANGES OR SMOKING?

The influence of sex hormone related events and smoking on thedevelopment of OA in women was investigated in a case-controlledpostal survey. One hundred and twenty-nine patients with nodalgeneralized osteoarthritis (NGOA) and 145 with non-nodal pauciarticularlarge joint osteoarthritis (LJOA) were identified from the databaseof a Nottingham OA clinic. For each patient, three age-matchedcontrols were randomly selected from the same general practice.Sixty-three per cent of questionnaires (690/1096) were returned:NGOA, 95; NGOA controls, 226; LJOA, 113; LJOA controls, 256.There were no differences in age at menarche or menopause, ratesof hysterectomy, oral contraceptive use, or hormone replacementuse between cases and controls. Fewer OA patients had ever smoked[(Odds Ratio (OR) 0.65, 95% Confidence Interval (CI) 0.45–0.95)]and subset analysis demonstrated that this negative associationoccurred only in the LJOA group (OR 0.43, CI 0.25–0.72),particularly in those with knee OA (OR 0.29, CI 0.14–0.62).A previous successful pregnancy was negatively associated withNGOA (OR 0.47, CI 0.24–0.95). This study demonstratess no association between oestrogen-relatedhormonal events and OA, but a negative association between smokingand LJOA. Such data supports the concept that OA is a heterogeneousdisease and underlines the need to differentiate OA subsets. KEY WORDS: Osteoarthritis, Hormonal changes, Smoking, Nodes     

Relation between Heberden's nodes and distal interphalangeal joint osteophytes and their role as markers of generalised disease

OBJECTIVE—Heberden's nodes are often used as a marker for osteoarthritis (OA). This study examined how often Heberden's nodes and radiological distal interphalangeal (DIP) osteophytes coexist in the same digit and the sensitivity, specificity, and positive predicative value of each for OA at different sites or generalised disease.
METHODS—This was a population-based study of 660 middle aged women taking part in a twin study of OA. Distal interphalangeal osteophytes were defined radiologically and graded on a four point scale (0-3) using a published atlas of individual features. Heberden's nodes were defined by standardised clinical examination. OA in other joints (knees, proximal interphalangeal (PIP) joints and carpometacarpal (CMC) joints) was defined radiologically using a published atlas.
RESULTS—Poor agreement was observed between a Heberden's node (HN) and a radiological distal interphalangeal osteophyte in the same finger of the same hand (κ statistic (95% CI) = 0.36 (0.33, 0.39)). Although HN and radiological DIP osteophytes had similar sensitivity, the specificity and positive predicative value of DIP osteophytes was considerably higher for detecting knee, CMC, PIP OA, and OA in more than two groups of joints (knee, CMC, and DIP joints).
CONCLUSION—HN are not synonymous with DIP osteophytes. Radiological DIP osteophytes are a better marker of knee and multiple joint OA than HN. HN may still be an imperfect surrogate for hand OA when radiology is impractical, but are not an accurate marker of generalised disease.

Keywords: Heberden's nodes; osteoarthritis; distal interphalangeal joint osteophytes     

Serum keratan sulfate. Quantitative and qualitative comparisons in inflammatory versus noninflammatory arthritides

The concentration of keratan sulfate (KS) epitope was measured in the serum of patients with osteoarthritis (OA) or rheumatoid arthritis (RA) by enzyme-linked immunosorbent assay and compared with that in the serum of patients with primary fibromyalgia syndrome (PFS) and of controls who had no joint disease. By Student's tau-test, the mean serum KS concentrations in OA and RA patients measured with monoclonal antibodies (MAb) 5-D-4 and 2-D-3 were significantly increased over those in the PFS and normal groups; similar findings were observed using a nonparametric test, except that levels in RA patients showed no difference from those in PFS patients and normal subjects. There was no significant correlation between joint scores or disease duration and KS levels in OA or RA patients. Gel filtration of sera revealed mainly large, polydisperse KS-bearing fragments which eluted in a broad profile. KS purified from sera by immunoaffinity chromatography consisted mainly of high-density proteoglycans. Electrophoresis of pooled high-density KS fractions in polyacrylamide-agarose gels followed by Western blotting with MAb 5-D-4 showed diffuse bands with relative mobilities corresponding to large proteoglycans. These findings are consistent with attachment of KS to protein core fragments of various sizes; KS in patient sera is comparable in size with that in normal sera. Elevations of serum KS levels occur in the presence of cartilage degradation, but do not quantitatively define the extent or duration of articular involvement.     

Synovial fluid concentrations of the C-propeptide of type II collagen correlate with body mass index in primary knee osteoarthritis

OBJECTIVE—To explore in a cross sectional study in patients with primary knee osteoarthritis (OA) the relations between body mass index (BMI), disease stage, and the concentrations of a putative joint fluid marker of type II collagen synthesis, procollagen II C-propeptide.
PATIENTS AND METHODS—The study included 142 patients with knee OA (median age 68, median BMI 24.1). OA was staged radiologically. The concentrations in synovial fluid of procollagen II C-propeptide were measured by a sandwich enzyme immunoassay.
RESULTS—Joint fluid concentrations of procollagen II C-propeptide were increased in knees with OA (median 3.7 ng/ml), compared with published reference values for knees in healthy adult volunteers (median 1.3 ng/ml). The concentrations of procollagen II C-propeptide were independently related to both OA stage and BMI (r_s = 0.343, p < 0.0001 and r_s = 0.253, p = 0.002, respectively).
CONCLUSIONS—Joint fluid concentrations of this putative marker of collagen II synthesis are high in early and mid-stage OA, but decrease in end stage disease. In addition and for the first time it was shown that the concentrations in synovial fluid of procollagen II C-propeptide increase with increasing BMI in primary knee OA. The increased joint fluid values of this marker in patients with primary knee OA and a high BMI, may reflect increased rates of collagen synthesis in their joint cartilage and could relate to the previously shown increased risk for disease progression in such patients.

     

Increased expression of human type IIa secretory phospholipase A2 antigen in arthritic synovium

OBJECTIVE—To determine the localisation and level of expression of human type IIa secretory phospholipase A₂ (sPLA₂) in the synovium of rheumatoid arthritis (RA), osteoarthritis (OA), and non-arthritic (NA) patients and to examine the relation between sPLA₂ and histological features of inflammation.
METHODS—Immunoperoxidase staining using the anti-sPLA₂ monoclonal antibody 9C1 was performed on frozen sections of knee synovium of 10 RA, 10 OA, and 10 NA patients. sPLA₂ positive cells were scored on a scale of 0-3 in 10 fields of a representative tissue section from each case. Double labelling imunofluorescence confocal microscopy with antibodies to CD14 or CD45 and 9C1 was used to determine cell type specificity. Inflammation was assessed by semiquantitative scoring of lining layer thickness and mononuclear cell infiltrates (MC) and a cumulative inflammation score, generated by summing the two parameters. Scores in each group were compared using non-parametric statistical analysis.
RESULTS—sPLA₂ was localised to endothelium (EC), vascular smooth muscle (VSM), and mast cells (M) in all tissue sections. In RA and OA sections, staining was seen in both macrophage-like and fibroblast-like cells in the synovial lining layer (LL) and subsynovial lining layer (SLL). Perineural cells stained positively. Subintimal lymphoid aggregates (LA) were negative in all sections. The RA group showed significantly greater staining in extravascular synovial tissue (median 3.6, range 1.5-6.0) than the OA (median 1.95, range 0-5.3) or NA (median 0, range 0-5.9) groups (p<0.05). LL staining was significantly higher in RA than both OA and NA sections (p<0.05). The OA group showed a trend to higher staining scores than the NA group that did not reach significance. There was a significant correlation between the sPLA₂ staining score and inflammation score within the RA patient group (p<0.05).
CONCLUSIONS—The synovium is a site of increased expression of sPLA₂ antigen in both RA and OA relative to NA. Its presence in both fibroblast and macrophage-like cells in the LL and SLL of synovial tissue in RA and OA, but not NA, indicates that the enzyme is specifically induced in these regions in both conditions with expression in the LL being particularly characteristic of RA. The widespread expression of sPLA₂ in synovium suggests it is likely to play a significant part in synovial pathology

Keywords: synovium; phospholipase A₂; immunohistochemistry; confocal microscopy     

T cell derived cytokines in psoriatic arthritis synovial fluids

OBJECTIVE—The aim of this study was to investigate the concentrations of T cell derived cytokines in the synovial fluids (SFs) of patients with psoriatic arthritis (PsA) in comparison with rheumatoid arthritis (RA) and osteoarthritis (OA).
METHODS—Th1 type cytokines (interleukin 2 (IL2), tumour necrosis factor β (TNFβ), and interferon γ (INFγ)) and Th2 type cytokines (IL4, IL10) were measured by means of enzyme linked immunosorbent assays.
RESULTS—IL2 was usually not detectable in any of the disease groups. TNFβ was found in 3 of 31 PsA SFs (mean (SEM) 11.1 (2.3) pg/ml) and in a significantly lower concentration than in 20 of the 40 RA SFs (42.2 (15.6) pg/ml; p < 0.002). INFγ was measurable in 2 of 10 PsA and 6 of 16 RA SFs (p > 0.05). IL4 was present at low concentrations in 4 of 22 PsA SFs (0.41 (0.8) pg/ml), and in 15 of 20 RA SFs (0.63 (0.09) pg/ml; p < 0.01). IL10 was found in 4 of 27 PsA SFs (12.3 (0.9) pg/ml) and in 27 of 32 RA SFs (37.3 (4.9) pg/ml; p < 0.0001). In all OA SFs cytokine concentrations were below the limit of detection.
CONCLUSION—The pattern of T cell derived cytokines in PsA SFs was similar to that of RA SFs. However, both the frequency and the concentrations of cytokines were lower in PsA SFs than in RA SFs, while OA SFs generally lacked any detectable T cell cytokines altogether. The presence of Th1 and Th2 cell derived cytokines in PsA SFs suggests the presence of activated T cells in the inflamed joint tissues and their participation in the immunoinflammatory events.

Keywords: psoriatic arthritis; rheumatoid arthritis; cytokines; T cells; synovial fluids     

Mutual antagonism of rheumatoid arthritis and hay fever; a role for type 1/type 2 T cell balance

OBJECTIVES—The balance between interferon γ(IFNγ) and interleukin 4 (IL4) producing T cells (T1 and T2 cells) seems to be of importance in many (auto)immune disorders. In general, T1 cell activity is important in cellular immunity whereas T2 cell activity plays a part in humoral responses. T1 cell activity predominates in joints of patients with rheumatoid arthritis (RA) whereas T2 cell activity is characteristic of atopic syndromes. This study investigated whether the prevalence of hay fever in RA is low and if severity of RA (T1 cell activity) can be influenced by the concomitant occurrence of a T2 cell mediated disease (hay fever).
METHODS—The prevalence of hay fever was assessed in 643 consecutive (RA and non-RA) patients seen in our outpatient clinic and confirmed by skin test and specific IgE. Of this group the 12 RA patients with hay fever were compared with RA patients without hay fever (matched for age, sex, and disease duration).
RESULTS—The prevalence of hay fever in RA patients is lower than in non-RA patients (4% versus 8%), and yields a relative risk for RA patients to develop hay fever of 0.48. RA patients with hay fever showed a lower disease activity (erythrocyte sedimentation rate, C reactive proten, Thompson joint score, and radiographic joint damage (Sharp) score) than RA patients without hay fever. The clinical data were related to peripheral blood T1/T2 cell balance: a lower IFNγ/IL4 ratio was observed for RA patients with hay fever, indicating a comparatively increased T2 cell activity in RA patients with hay fever.
CONCLUSION—These results argue in favour of the exploration of treatments aimed at regulation of a possible imbalance in T1/T2 cell activity in RA.

Keywords: rheumatoid arthritis; hay fever; T1 T cell; T2 T cell; interferon γ; interleukin 4     

Biomarkers of incident radiographic knee osteoarthritis: Do they vary by chronic knee symptoms?

Objective

To explore the ability of osteoarthritis (OA)–related biomarkers to predict incident radiographic knee OA in a large sample of African American and Caucasian men and women.

Methods

Baseline levels of serum cartilage oligomeric matrix protein (COMP), hyaluronan (HA), high‐sensitivity C‐reactive protein (hsCRP), and keratan sulfate (KS) and baseline and followup radiographs were available for 353 knees without baseline osteophyte formation and for 446 knees without baseline joint space narrowing (JSN). Cox models estimated the hazard ratio (HR) and 95% confidence interval (95% CI) for incident knee OA for a 1‐unit increase in the ln of each biomarker, with adjustment for age, race, sex, body mass index, and knee OA of the contralateral limb. Report of chronic knee symptoms was explored as a modifier of the association.

Results

The hazard of incident knee osteophytes (HR 2.16 [95% CI 1.39–3.37]) and incident JSN (HR 1.82 [95% CI 1.15–2.89]) increased with higher baseline ln(COMP) levels. The hazard of incident knee JSN increased with higher ln(HA) levels (HR 1.46 [95% CI 1.14–1.87]). Baseline ln(hsCRP) and ln(KS) did not predict incident knee outcomes. HRs per unit increase in ln(COMP), ln(HA), and ln(KS) were higher among knees with chronic symptoms than among those without symptoms.

Conclusion

Higher baseline ln(COMP) and ln(HA) levels were associated with incident knee OA over an average followup period of 6.3 years. These results represent detection of a molecular stage of OA prior to radiographic manifestations. Further exploration is needed to determine how chronic knee symptoms modify the biomarker–incident knee OA association.