ANA Levels Research Articles

Presence and distribution of PAHs, PCBs and DDE in feed and sediments under salmon aquaculture cages in the Bay of Fundy, New Brunswick, Canada

1. Wastes from feed and faeces can result in the deposition of contaminants in sediments around aquaculture sites. Five types of feed pellet, a commercial fish oil and 76 sediment samples collected under and up to 100 m away from salmon aquaculture cages in the south-western Bay of Fundy between 1998 and 2000 were analysed for polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and chlorinated pesticides. 2. Five alkylated naphthalenes (aNAs) were consistently detected in fish oil (116–180 ng g−1, per aNA), in pellets (25–51 ng g−1, dry weight, per aNA), and sediments (<1–45 ng g−1, dry weight, per aNA). Other PAHs were detected at variable levels in feed or in sediments. 3. IUPAC congener 153 (a PCB) and p,p′-dichlorodiphenyldichloroethylene (p,p′-DDE) were detected more frequently than other chlorinated targets in oil (108 ng g−1 and 176 ng g−1 respectively), feed (<1–14 ng g−1 and 1.7–28.2 ng g−1 respectively) and sediments (<0.08–3 ng g−1 and <0.5–7 ng g−1 respectively). 4. Trends were observed during the first year of sediment sampling (1998), with higher organic carbon, PCBs and p,p′-DDE levels below the cages than 50 m away. The PAHs other than aNA showed an opposite trend with distance. In 1999, levels of p,p′-DDE and PCBs were somewhat reduced under the cages, but were detected up to 100 m away from the cages. 5. Levels of aNA tended to be higher at some sites in 1999 relative to 1998, reflecting variability in feed and/or differential transport or degradation of contaminants relative to the environmental background. When detected, mean levels of PCBs and DDE were 2–10 times lower in 2000 than in 1999, and PAHs were 30–40% lower in 2000 than in 1999. 6. Interpretation of the results is done cautiously, since the exact locations of the sites sampled is only known to an intermediate facilitating the work between farmers and scientists. Levels of contaminants are compared with international results, interpreted relative to potential toxicity, uptake from feed, from deposited sediments, and in the framework of an aquaculture decision-support system published recently. Copyright © 2005 John Wiley & Sons, Ltd.

Germinal Centres in Primary Sjögren's Syndrome Indicate a Certain Clinical Immunological Phenotype

Ectopic germinal centers (GCs) can be detected in the salivary glands of approximately 1/5 of patients with Sjögren's syndrome (SS) and appear in both primary and secondary SS. Previously, ectopic GC have been associated with increased local autoantibody production. The aim of this study was to determine whether GC in primary Sjögren's syndrome (pSS) defines a distinct seroimmunological phenotype. Retrospectively, a material of 130 haematoxylin and eosin‐stained paraffin‐embedded tissue sections of minor salivary gland tissue from patients with pSS was morphologically screened for the presence of ectopic GC. GC‐like lesions were detected in 33/130 (25%) of the pSS patients. Seventy‐two pSS patients lacking these structures (GC‐) were randomly selected for comparison. Focus score was significantly increased in the GC+ patients compared to the GC– patients (P = 0.035). In the GC+ group, 54.5% of the patients presented with anti‐Ro/SSA compared to 43.7% in the GC– group. Anti‐La/SSB was detected in 31.3% of the GC+ patients compared to 25.7% of the GC– patients. Sixty‐one percentage of GC+ patients presented with increased levels of IgG, a nonsignificant difference when compared to 39.4% in the GC– patients (P = 0.089). Levels of RF, ANA, ENA, IgM and IgA were similar in both patient groups, as were ESR and CRP. In conclusion, patients with ectopic GC have a higher focus score and more often present with autoantibodies and increased levels of IgG compared to pSS patients with regular focal infiltration (GC–). Our findings may indicate a certain seroimmunological phenotype and warrant for further prospective studies.

Clinical laboratory experience with enzyme immunoassays for the detection of auto-antibodies to nuclear antigens

Objective: We introduced enzyme immunoassays (EIAs) for detecting auto-antibodies to nuclear antigens in 1999 and discontinued testing for these autoantibodies (including anti-nuclear antibodies, ANA) by indirect fluorescence microscopy. During the past year, we monitored the performance of the new EIA assays to determine their reliability, and to validate the decision to switch to EIA methodology.Methods: Tests for ANA, anti-dsDNA, and anti-DNA antibodies (screening and discrete assays) were performed by EIAs according to the manufacturer's recommended procedures (Helix Diagnostics Inc., West Sacramento, CA). Results were scored as follows: for ANA: <1 U, negative; 1–3 U, weakly positive; 3–6 U positive; and >6 U, strongly positive; and, for anti-dsDNA <25 U, negative; 25–30 U, borderline; and >30 U, positive; and for anti-ENA: <20.0 U, negative; 20–25.9 U, borderline; and >26.0 U, positive. For the calendar year 2000, we monitored the frequencies of negative, weakly positive, positive and strongly positive ANA results for all sera submitted for testing across 3 different lots of kit reagents. We also evaluated a study group of 518 sera from patients seen locally that were positive or borderline positive for the presence of anti-ENA antibodies on the screening assay. For this group of test results, we calculated the frequencies of each discrete positive ENA specificity, and the frequencies of positive anti-dsDNA and ANA results.Results: The ANA test was very stable from lot-to-lot. The month-to-month frequencies for ANA results in each category were as follows: negative, 70+ or −4.1%; weakly positive, 19+ or −1.8%; positive, 6+ or −0.9%; and strongly positive, 4+ or −0.7%. For the 7 months period from January through July, 2000, the cumulative frequency of positive and borderline results for the ENA screen assay for patients seen locally was 11.0%. ANA test results were available in 391 of 518 sera with borderline or positive ENA screen results. The ANA was >1 U in 93% of these cases, and >3.0 U in 76% of cases. In no case did we find a positive anti-dsDNA result in a specimen that had an ENA screen result >20 U and an ANA result <1 U. The vast majority of positive anti-dsDNA results (94%) were observed in sera that had ANA results >6 U. Similarly, the frequencies of positive anti-ENA antibodies varied directly with the level of ANA: 80% of positive ENA results occurred in sera with ANA levels >3.0 U and 63% had levels >6.0 U. The ENA screen assay performed well in identifying sera that one or more discrete ENA antibodies: 87% of sera had at least one positive discrete ENA result and 100% of sera had at least one discrete ENA result >20 U. The frequencies of individual ENA antibody specificities varied widely in sera that were presumptively positive for ENA antibodies on the screening assay. The individual frequencies were as follows: anti-SSA, 59%; anti-SSB, 22%, anti-Sm/RNP, 9%; anti-RNP, 27%; anti-Scl 70, 12%; and anti-Jo 1, 6.3%Conclusions: Each of the EIA assays mentioned above performed well in day-to-day clinical practice. The results indicate that the ANA and ENA screening assays are reliable for detecting the presence of antibodies to dsDNA and discrete ENA antigens, respectively. The finding of a direct correlation between the level of ANA and the presence of anti-dsDNA or ENA antibodies confirms the reliability of the ANA EIA as a screening test for marker auto-antibodies.

Organ and Non-organ Specific Autoantibody Titres and IgG Levels as Markers of Disease Activity: A Longitudinal Study in Childhood Autoimmune Liver Disease

No longitudinal study has investigated whether autoantibody titres and serum IgG levels correlate with disease activity in autoimmune liver disease. To determine this, we investigated prospectively 19 patients on 254 occasions between 10 months to 5 years from diagnosis. Nine had anti-nuclear and/or anti-smooth muscle antibody (ANA/SMA) positive autoimmune hepatitis (type 1 AIH), 5 liver kidney microsomal type 1 (LKM-1) positive AIH (type 2 AIH) and 5 ANA/SMA positive autoimmune sclerosing cholangitis (ASC). Correlation between IgG levels, titres of ANA, SMA and LKM-1 and levels of the organ specific autoantibodies anti-liver specific protein (anti-LSP), and anti-asialoglycoprotein receptor (anti-ASGPR) with biochemical evidence of disease activity, as measured by serum aspartate amino transferase (AST) levels, was sought during the course of the disease. AST levels correlated with levels of anti-LSP, anti-ASGPR and IgG in type 1 and 2 AIH, but not in ASC. Positive correlation with AST was also observed for LKM-1 titres in type 2 AIH and for SMA titres in type 1 AIH, but not in ASC. In both AIH and ASC, AST levels correlated with the T cell-dependent immune responses anti rubella IgG and anti tetanus toxoid IgG, but not with the T cell-independent IgG 2 response to pneumococcal capsular polysaccaride. Our results indicate that measurement of organ and non-organ specific autoantibodies and IgG levels may be used to monitor disease activity in AIH.

ANCA-assoziierte kutane Vaskulitis in der Schwangerschaft

Bericht über eine 28-jährige Patientin, bei der in der 26. Schwangerschaftswoche (SSW) bullös-hämorrhagische Läsionen an den Oberarmen und Beinen auftraten, die histologisch Zeichen einer leukozytoklastischen Vaskulitis aufwiesen. Unter einer kurzzeitigen intravenösen Prednisolontherapie bildeten sich die Hauterscheinungen völlig zurück. In der 33. SSW erneute Krankheitszeichen mit Ausbildung multipler nekrotischer Hautbezirke an den Extremitäten. Zusätzlich fielen eine Thrombozytose (721Gpt/l) und stark erhöhte Werte für ANA, c-ANCA (Proteinase 3), p-ANCA (Myeloperoxidase) sowie für ds-DNA und n-DNA auf. Es bestand jedoch keine Organbeteiligung. Die Behandlung erfolgte initial mit 175 mg Prednisolon pro Tag. In der 38. Schwangerschaftswoche Geburt eines gesunden Mädchens nach vorzeitiger Weheneinleitung. Die Abheilung der Läsionen erfolgte innerhalb eines halben Jahres post partum unter ausschleichender Glukokortikoidbehandlung. Zur Erklärung der Pathogenese dieser Vaskulitis wurde die „ANCA-Zytokin-Sequenztheorie” herangezogen.

Risk factors for central nervous system involvement in systemic lupus erythematosus.

We investigated risk factors for central nervous system (CNS) involvement in systemic lupus erythematosus (SLE), in 32 such patients individually matched 1 : 3 to 96 control SLE patients without CNS events. Univariate analysis showed that CNS involvement was significantly associated with the antiphospholipid syndrome (APS) as well as its features: arterial thrombosis, recurrent fetal loss, livedo reticularis and IgG anticardiolipin (aCL) antibodies in high titres. Other potential associations included cutaneous vasculitic lesions, thrombocytopenia, positive ANA, anti-SS-B/La and low serum levels of C(3) and C(4) complement components, while articular manifestations and discoid rash were significantly less common in patients with neuropsychiatric (NP) disease. In multivariate modeling, CNS involvement was strongly associated with cutaneous vasculitic lesions OR 33, 95% CI 1.5-720) and arterial thromboses (OR 13, 95%CI 0.82-220), and negatively related to the presence of articular manifestations (OR 0.015, 95%CI 0.00-0.17) and discoid rash (OR 0.004, 95%CI 0.00-0.35). Associations with APS-related arterial thromboses and vasculitis point to the importance of arterial vascular pathophysiology in the pathogenesis of NP disease in SLE. Patients with articular manifestations and discoid rash are at very low risk of NP events. Patients with an adverse SLE disease profile may require closer observation and may be the target group for studying pre-emptive interventions.

Autoimmune aberration in sudden sensorineural hearing loss: association with anti-cardiolipin antibodies.

In view of the presence of autoantibodies against inner ear antigens, the pathogenesis of sudden deafness (SD) and progressive sensorineural hearing loss (PSNHL) is suggested to be of an autoimmune nature. However, microthrombosis of the inner ear may result from pathogenic anti-cardiolipin antibody (aCL) activity. We studied 30 patients (17 females and 13 males, age range 20-52 y), of whom 11 suffered from SD and 19 from PSNHL. All were clinically and serologically evaluated for association with autoimmune disorders (serological examination included: aCL, ANA, ENA, ANCA, proteinelectrophoresis, and complement levels). Twenty healthy matched subjects served as controls. None of the control group were aCL positive, whereas 8 out of 30 (27%) patients demonstrated low-moderate titers (P < 0.02), of whom 5 out of 8 suffered from SD. In addition, 2 aCL negative patients with PSNHL demonstrated hypergammaglubolinemia accompanied by hypocomplementemia, whereas none with SD had such abnormalities. Our data suggests that aCL is detected in patients with sudden sensorineural hearing loss and therefore may play an important role in the pathogenesis of this disability. If sustained by additional studies, these findings would warrant the consideration of anticoagulant therapy.

Monoamines and the release of gametes by the scallopArgopecten purpuratus

Levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were measured fluorometrically in the ganglia, gonads and adductor muscle of the functionally hermaphroditic scallop Argopecten purpuratus at different times during the induced release of gametes. The levels of these amines were analyzed in samples before stimulation, when animals looked stimulated, during the release of sperm, during the release of oocytes, and 24 hours after the end of spawning. Levels in muscles of the three monoamines changed during spawning and the greatest change was detected in the level of NA. In nervous tissue, the level of 5-HT decreased, whereas those of DA and NA increased significantly with the release of sperm. In both the female and male portions of gonad, levels of DA and NA increased during spawning while those of 5-HT decreased. However, levels of 5-T in the female portion of gonads did not show any changes in a group of scallops that did not release sperm before releasing oocytes. Separate analysis of levels of monoamines in the visceral ganglion from those in the cerebropedal ganglion, showed that, in spawning animals, levels of DA and ANA did not change in cerebropedal ganglia but decreased in the visceral ganglia, whereas levels of 5-HT decreased only n the cerebropedal complex. The results are consistent with the existence of two different mechanisms for the control of the release of sperm ad oocytes by hermaphroditic pectinids. © 1996 Wiley-Liss, Inc.

Monoamines and the release of gametes by the scallop Argopecten purpuratus

Levels of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) were measured fluorometrically in the ganglia, gonads and adductor muscle of the functionally hermaphroditic scallop Argopecten purpuratus at different times during the induced release of gametes. The levels of these amines were analyzed in samples before stimulation, when animals looked stimulated, during the release of sperm, during the release of oocytes, and 24 hours after the end of spawning. Levels in muscles of the three monoamines changed during spawning and the greatest change was detected in the level of NA. In nervous tissue, the level of 5-HT decreased, whereas those of DA and NA increased significantly with the release of sperm. In both the female and male portions of gonad, levels of DA and NA increased during spawning while those of 5-HT decreased. However, levels of 5-T in the female portion of gonads did not show any changes in a group of scallops that did not release sperm before releasing oocytes. Separate analysis of levels of monoamines in the visceral ganglion from those in the cerebropedal ganglion, showed that, in spawning animals, levels of DA and ANA did not change in cerebropedal ganglia but decreased in the visceral ganglia, whereas levels of 5-HT decreased only n the cerebropedal complex. The results are consistent with the existence of two different mechanisms for the control of the release of sperm ad oocytes by hermaphroditic pectinids. © 1996 Wiley-Liss, Inc.

Effects of anandamide (endogen cannabinoid) on anterior pituitary hormone secretion in adult ovariectomized rats

It has been shown that the main psychoactive component of marihuana, Δ 9-tetrahydrocannabinol (THC) has mainly inhibitory effects on pituitary luteinizing hormone (LH), prolactin (PRL) and growth hormone (GH) and has no or little effect on follicle stimulating hormone (FSH) secretion. Recently the purification and availability of the putative endogenous ligand for the cannabinoid receptor, anandamide (arachidonyl ethanol-amide, anandamide) (ANA) provided us the opportunity to compare the effects of THC and ANA on the female neuroendocrine system in ovariectomized (OVX) rats. OVX was performed three weeks prior to the experimental period to avoid cyclic differences. OVX rats were injected i.p. with either THC or ANA (0.02mg/kg.b.w./day, respectively) or vehicle for two weeks. The results show that both ANA and THC decrease serum LH level although THC with a higher degree. No significant differences were observed in serum FSH level. Both drugs decreased serum PRL. Serum GH was increased after THC administration and significantly decreased after ANA. The results indicate that ANA and THC alter pituitary hormone secretion, mainly by inhibitory action. The site of action requires further investigations.

Higher salt consumption, digoxin-like factor, and nifedipine response are associated with salt sensitivity in essential hypertension.

In addition to demonstrating evidences of increased sympathetic nervous system activity and marked left ventricular hypertrophy in salt-sensitive hypertensives, our group has also reported increased weight gain with salt overload in these patients. The increased weight gain suggests volume expansion, a situation already shown to increase plasma levels of a Na, K-ATPase inhibitor. Therefore, in the present study, digoxin-like factor (DLF) serum levels, spontaneous salt ingestion, nifedipine hypotensive effect, and plasma renin activity were evaluated in essential hypertensive subjects. Thirteen essential hypertensive outpatients were studied sequentially on an ad lib diet, a low salt diet (LSD = 30 mEq Na/day), and a high salt diet (HSD = LSD + 171 mmol/L NaCl/day), 1 week each. On the seventh day of LSD and HSD, DLF levels, mean blood pressure (MBP) response to nifedipine (10 mg sublingual), and plasma renin activity were measured. The MBP percent change from the seventh day of LSD to the seventh day of HSD (salt sensitivity) ranged from -13.7 to 20.9%. A positive correlation (r = 0.64, P < .01) was observed between salt sensitivity and 24-h urinary sodium excretion with an ad lib diet. The DLF serum levels correlated with the salt sensitivity both on LSD (r = 0.50, P < .05) and on HSD (r = 0.53, P < .05). Salt sensitivity was positively correlated with the difference of response to nifedipine between HSD and LSD (r = 0.78, P < .001). Plasma renin activity correlated inversely with DLF on LSD (r = -0.51, P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Polyclonal B-cell activation is related to exocrine manifestations of primary Sjögren's syndrome

Twenty-four female and four male patients with primary Sjögren's syndrome were examined in order to evaluate possible correlations between the exocrine disease manifestations and polyclonal B-cell activation parameters. All patients were examined three times over a 4-month period and none of them received any systemic medical treatment. Van Bijsterveld scores were negatively correlated to unstimulated whole salivary flow rate (sialometry) values ( P<0.01) and break-up times (BUT) ( P<0.01), while unrelated to Schirmer-1 values. Unstimulated sialometry values were, in addition, positively correlated to Schirmer-1 values ( P<0.01), while BUT were unrelated to Schirmer-1 and unstimulated sialometry values. P-IgG levels were positively correlated to van Bijsterveld scores ( P<0.01) and negatively correlated to break-up times ( P<0.05), while unrelated to unstimulated sialometry and Schirmer-1 values. P-IgG levels were furthermore positively correlated to levels of P-IgM ( P<0.05), P-IgA ( P<0.05), serum IgM-RF ( P<0.001) and serum ANA ( P<0.01). Levels of P-IgM-RF were positively correlated to van Bijsterveld scores ( P<0.01), but to none of the other exocrine manifestations. We conclude that the plasma levels of B-cell products seem to correlate positively with the degree of ocular involvement in patients with primary Sjögren's syndrome, indicating a relationship between the immunoinflammatory processes and the mucosal damage.

Dry eyes or mouth—An epidemiological study in Swedish adults, with special reference to primary Sjögren's syndrome

The prevalence of dry eyes or dry mouth, and of primary Sjögren's syndrome (primary SS) according to the Copenhagen criteria were established in 705 randomly selected subjects, aged 52–72 years who answered a simple questionnaire, and of whom 247 (35%) reported symptoms. A sub-group with symptoms ( n=77) and a matched asymptomatic control group ( n=32) were examined with the Schimer-1 test (S1t), tear film break-up time (BUT), van Bijsterveld score (vB), unstimulated whole sialometry (Sialo) and, in about 40% of them labial salivary gland (LSG) biopsy and salivary gland scintigraphy. Apart from four cases of keratoconjunctivitis sicca (KCS) among controls, cases of KCS (15), xerostomia (12), autoimmune sialoadenitis (6) and primary SS (6) were exclusively confined to the symptomatic group. The calculated frequencies (with 95% confidence intervals) for the whole population were 14.9 (7.3–22.6)% for KCS, 5.5(3.0–7.9)% for xerostomia and 2.7 (1.0–4.5)% for autoimmune sialoadenitis and primary SS. The serum levels of ANA and RF were similar in the two groups, though those of anti-SS-B/La antibodies were higher in the group with symptoms ( P < 0.01).

Changes in the cervical spine in chronic polyarthritis

In 93 patients with classical chronic polyarthritis (rheumatoid arthritis) (at least five ARA-criterias) there were inflammatory lesions of dens epistropheus in 48.4%, ventral atlantoaxial subluxations in 25.8%, lateral atlantoaxial dislocations in 14% and pseudobasilary invagination in 5.4%. Step-ladder-subluxation between C 2/C 7 was found in 31.2%, discitis in 12.5% and spondylarthritis in 38% of cases. Inflammatory signs of the cervical spine were correlated to the Steinbrocker-Grade IV, ANA level 1:40 and the degree of Waaler-Rose. The correlation between long standing steroid-therapy and signs of cervical involvement during c.p.--specially in C1/C2--is found to be proven. There are connections between the duration of c.p. (more than 10 years) and manifestation of cervical spine lesions, further, in a protective sense between longstanding gold therapy and cervical spine lesions.

Humoral immunologic abnormalities in workers exposed to asbestos cement dust

Serum specimens from 144 workers exposed to asbestos cement dust were examined for the presence of ANA, RF, immunoglobulins, and IC. These immunologic findings were compared with chest radiographic changes. A high percentage of workers had polyclonal hypergammaglobulinemia, and there was a statistically significant association between elevated levels of IgC and IgM and radiographic classification. Although a significant number of workers had an increased prevalence of ANA and elevated levels of IC, there was no correlation between these parameters and chest radiographs. These findings support B cell hyperactivity in workers exposed to asbestos and suggest that autoantibody production and IC are not directly involved in disease pathogenesis.

A circulating inhibitor of (Na+ + K+)ATPase associated with essential hypertension.

The aetiology of essential hypertension, a disease prevalent in cultured societies, is unknown. However, much evidence suggests that abnormal sodium metabolism has a critical role—this has led to the hypothesis that an increase in the circulating concentration of an inhibitor of (Na+ + K+) ATPase is responsible for the increased peripheral vascular resistance in essential hypertension1. Evidence for relatively high levels of a Na+ pump inhibitor in essential hypertension has come from bioassay and cytochemical assays of plasma and urine from normotensive and hypertensive individuals2,3. There is also evidence for increased plasma levels of a Na+ pump inhibitor in some animal models (for example, renal and deoxycorticosterone acetate (DOCA) models) of hypertension4. Nevertheless, direct biochemical determination of (Na+ + K+) ATPase inhibition by this substance has not yet been reported. We demonstrate here, with a kinetic (Na+ + K+) ATPase assay, a highly significant correlation between levels of a plasma inhibitor of (Na+ + K+)ATPase activity and mean arterial blood pressure (MAP) in normotensive and hypertensive individuals. These data provide evidence for the involvement of a circulating Na+ pump inhibitor in the genesis of essential hypertension. Moreover, our assay methods may be useful for the isolation and characterization of this inhibitor.

Antinuclear antibodies (ANA) in inflammatory eye diseases

The occurrence of antinuclear antibodies was investigated in patients with chronic open-angle glaucoma, senile cataract and retinal detachment, using the indirect immunofluorescence technique. The values obtained were the same as those for a normal population. Additionally, the presence and titer levels of ANA were tested in patients with endogenous uveitis, papillitis and optic neuritis. Our results suggest that ANA do not occur more frequently in these conditions.

Prospective study of the early course of rheumatoid arthritis in young adults: Comparison of patients with and without rheumatoid factor positivity at entry and identification of variables correlating with outcome

The early course of newly diagnosed RA among young adult patients (16-44 yr) is described from results of an ongoing study with a mean follow-up of 3.4 yr. Study diagnosis was based on the judgement of experienced rheumatologists, and data on several hundred variables were obtained on entry and annually for the purpose of defining patterns of onset and course of disease. Race and sex factors, as well as certain entry manifestations, e.g., RF, were found to correlate with onset and course patterns. Females, and especially white females, had significantly greater numbers of swollen upper extremity joints than males at entry and at last observation, with increased likelihood of developing bone erosions. At entry, RF positive patients differed only on few articular manifestations from RF negative patients, but had a higher frequency of positive ANA at entry and more subcutaneous nodules and bone erosions during follow-up. Seropositive white females at entry had significantly more swollen upper joints than their seronegative counterparts, but with no difference found at last follow-up. White females of each serogroup had more joint involvement at last examination than patients of other race-sex groups. Males had more acute onset, especially under age 30, with significantly greater improvement in arthritis and in ESR than did females. The majority (55%) of patients entered as seropositive, converted to seronegative during follow-up, and no correlation of either joint swelling or erosions was noted with this phenomenon. At last visit, RF positively did not correlate with bone erosions, but patients developing bone erosions had higher frequency of ANA and higher mean serum complement levels at last examination. The following entry factors were found to correlate significantly with a better outcome: maleness, acute onset under age 30, less swollen upper joints, and negative RF. Type of drug therapy tended to reflect severity of arthritis, rather than vice versa, and functional capacity improved significantly from entry to last evaluation in both males and females, even though the latter had stable or progressive arthritis. Further study is necessary over long intervals and in wider age range to more adequately interpret the biologic implications of findings of this ongoing study. A better understanding of the pathogenesis of RA may be derived from critical studies of the contribution of host factors, e.g., sex, and other variables predisposing to the development of RF positivity (and ANA), subcutaneous nodules, and bone erosions, particularly in systematic ongoing studies of patients with early diagnosed disease.