The association of variant mannose-binding lectin genotypes with radiographic outcome in rheumatoid arthritis.

OBJECTIVE: To investigate the possible association of mannose-binding lectin (MBL) genotypes with the outcome of rheumatoid arthritis (RA). METHODS: MBL genotypes and plasma concentrations were retrospectively determined in 140 RA patients who were selected from a major cohort followed up prospectively for up to 32 years. RESULTS: MBL-insufficient patients (those with 2 defective structural MBL alleles or with 1 defective allele combined with a low-expression variant of the normal allele) had unfavorable outcomes. The relative risk of a severe radiographic outcome event (30% of maximum radiographic destruction, or an RE30) was 3.1 (95% confidence interval 1.8-5.1) in the MBL-insufficient group versus the MBL-competent group (P < 0.0001). An RE30 occurred in 50% of MBL-competent patients within 17 years, while such an event occurred 9 years earlier in MBL-insufficient patients (i.e., within 8 years) (P < 0.0001). During the first 15 years, there was a significant trend toward lower hemoglobin levels (P < 0.04), higher erythrocyte sedimentation rates (P < 0.02), and a higher number of swollen joints (P < 0.05) in the MBL-insufficient group. CONCLUSION: MBL genotypes giving rise to MBL insufficiency are highly significant risk factors for fast progression of radiographic joint destruction.

Inflammatory patterns in rheumatoid arthritis estimated by the number of swollen and tender joints, the erythrocyte sedimentation rate, and hemoglobin: longterm course and association to radiographic progression.

OBJECTIVE: To investigate the association of individual plots and time-integrated values of repeated measures of inflammatory variables with radiographic outcome in rheumatoid arthritis (RA). METHODS: In 112 patients with RA, examinations of joint swelling and joint tenderness of 68 joints, and measurement of hemoglobin (Hb) and erythrocyte sedimentation rate (ESR) were performed each year for up to 22 years after the first visit. For each of these 4 variables, the patients were divided arbitrarily into 5 characteristic subgroups by means of inspection of individual plots of longitudinal observations of the variables and divided into 5 other subgroups according to 20% percentiles of the cumulative mean values of the variables. The outcome of the subgroups was evaluated by varying degrees of radiographic events estimated by Larsen scoring of consecutive radiographs of 46 joints. RESULTS: An increasing number of radiographic events in subgroups with increasing severity (increasing values of joint swelling, joint tenderness, and ESR, decreasing values of Hb) was seen for both the arbitrary subgroups and the percentile subgroups of joint swelling, Hb, and ESR, whereas the association of joint tenderness to radiographic progression was weak. CONCLUSION: A highly significant association between inflammatory variables and radiographic outcome could be observed, indicating that the degree of inflammation is important for the development of destructive joint damage in RA.

Radiographic progression in rheumatoid arthritis: a long-term prospective study of 109 patients.

OBJECTIVE: To investigate the long-term radiographic course as a mathematical function of disease duration in individual patients and in a group of patients with rheumatoid arthritis (RA). METHODS: In 109 patients with RA, radiographic examinations of 46 diarthrodial joints were performed at regular intervals of 1-3 years, for up to 30 years after disease onset. RESULTS: Five main types of progression were identified: 1) a rare type (<1%), with no radiographic progression at all; 2) a type with a slow or moderate onset, but an increasing progression rate (9% exponential growth type and 30% linear type); 3) a type with a moderate-to-fast onset and a stable progression rate (the square-root type; 11%); 4) a type with a fast onset, but a later decreasing progression rate (the first-order kinetics type, 30%); and 5) a type characterized by slow onset, then acceleration and later deceleration (the sigmoid type, 20%). CONCLUSION: The progression of radiographic damage in RA followed mathematical functions of time. The identification of progression type may be used in the prediction of outcome in patients with RA.

Mannan binding lectin in rheumatoid arthritis. A longitudinal study.

OBJECTIVE: Low serum levels of mannan binding lectin (MBL) are associated with increased risk of recurrent infections. We determined whether there was an association between serum MBL levels and the course and prognosis of rheumatoid arthritis (RA). METHODS: MBL was analyzed in sera from 99 patients with RA who were included in a longterm prospective study. RESULTS: Compared with controls, a high fraction of patients lacked detectable MBL in serum (11 vs 3%; p = 0.025). Comparing patients with MBL serum levels above and below the median revealed that those with levels below the median were younger at onset of RA (p = 0.043) and had higher erythrocyte sedimentation rate (p = 0.006), joint swelling score (p = 0.019), limitation of joint motion score (p = 0.027), and annual increase in radiographic destruction score (p = 0.053). CONCLUSION: MBL insufficiency may be a contributing pathogenetic factor in RA.

On the course of seropositive rheumatoid arthritis during and after long-term gold therapy.

The purpose of the present study was to get an estimate on the course of seropositive RA in 93 patients, who had been in chrysotherapy for at least 3 years up to 13 years. The study was observational with assessment once a year by the same physician. After one year the median number of swollen joints had decreased from six to two (p = 0.0001), and the median number of tender joints from five to two (p = 0.0001). This improvement was maintained throughout the period. A decrease in median erythrocyte sedimentation rate from 34 mm/h to 15 mm/h remained significant for 10 years, although the ESR gradually increased throughout the period. An increase in median hemoglobin from 7.8 mmol/l to 8.5 mmol/l lasted for 7 years. Contrastingly, the number of joints with limited motion increased from a median score of 4 to a median score of 20 (p = 0.0001). Radiographical changes progressed from a median score of 18 to a median score of 84 (p = 0.0001). Significant correlations were found between the ESR, joint tenderness score and limitation of motion score at the year 1, and later progression of limitation of motion score, but too weak to be of predictive importance. In conclusion early symptomatic improvement of rheumatoid arthritis during gold treatment can be stable during several years, but progression in the number of joints with limited motion and radiographical changes continues.

Seropositive rheumatoid arthritis in monozygotic twin sisters carrying HLA-DR4 or DR4 associated with B27.

We have followed 3 pairs of monozygotic twin sisters with seropositive rheumatoid arthritis (RA) since 1966, 1971 and 1975. RA developed in the probands at the age of 25, 39 and 21 years and in the cotwins 37, 8 and 19 years later, respectively. Two pairs, Nos 1 and 3, were discordant when first seen. Only Pair 1 had a family history of RA. Onset of RA was not related to marital status or pregnancy. It was improbable that contagious infections of childhood or seasonal infections could be important triggers of RA. Since the concordance rate for RA in monozygotic twins depends on the duration of the observation period, the previously stated concordance rate of 30% may be questioned.

Waaler Rose titres may decrease but increase again during chrysotherapy.

In 62 patients with seropositive rheumatoid arthritis, treated with gold compounds, the relationship between serological and clinical response was analysed, based on data on the rheumatoid factor (RF) titre, ESR, number of swollen joints and joint tenderness, through 3 years. Three groups were distinguished. The RF titre became normal in 19, remained elevated in 22, became normal and subsequently again elevated in 21. Responders and non-responders to chrysotherapy occurred in all 3 groups. The findings suggest involvement of pathogenetic mechanisms related to IgM-RF, and of pathogenetic mechanisms which are not related to IgM-RF, and which may be responsive or unresponsive to chrysotherapy.