Altered circadian rhythms in rheumatoid arthritis patients play a role in the disease's symptoms.

The circadian changes in the metabolism or nocturnal secretion of endogenous corticosteroids (reduction) observed in rheumatoid arthritis (RA) patients are responsible, in part, for the time-dependent changes that are observed in the inflammatory response and related early morning clinical symptoms of the disease. Melatonin (MLT), another circadian nocturnal hormone that is the secretory product of the pineal gland, has been implicated in the time-dependent RA inflammatory reaction with effects that are opposite to those of corticosteroids. As a consequence, altered functioning of the HPA axis (early morning reduced corticosteroid production) and of the pineal gland (night increased MLT production) found in RA patients, seem to be important factors in the appearance and perpetuation of the clinical circadian symptoms of the disease. Consistently, human proinflammatory Th1-type cytokine production (related to MLT stimulation) exhibits a diurnal rhythmicity with peak levels during the night and early morning, at a time when plasma cortisol (inducing the Th2-type cytokine production) is lowest and MLT is highest. Reduced daily light exposure as observed in northern Europe (Estonia), at least during the winter, might explain the higher and more prolonged serum MLT concentrations that were observed in northern RA patients, as well as some epidemiological features versus southern Europe patients.

Circadian melatonin and cortisol levels in rheumatoid arthritis patients in winter time: a north and south Europe comparison.

BACKGROUND: Altered functioning of the hypothalamic-pituitary-adrenal axis and altered melatonin production might modulate the circadian symptoms in patients with rheumatoid arthritis. OBJECTIVE: To investigate the influence of different winter photoperiods on the circadian rhythms of serum melatonin, cortisol, tumour necrosis factor alpha (TNFalpha), and interleukin 6 (IL6) in patients with rheumatoid arthritis from a north Europe country (Estonia) and a south Europe country (Italy). METHODS: The patients from Estonia (n = 19) and Italy (n = 7) had similar disease severity and duration and were compared with healthy age and sex matched controls in the two countries. Blood samples were collected during the period January to February at 8 pm, 10 pm, midnight, 2 am, 4 am, 6 am, 8 am, and 3 pm. Melatonin was measured by radioimmunoassay using (125)I-melatonin. Serum cortisol, TNFalpha, and IL6 cytokines were assayed by standard methods. RESULTS: Higher circadian melatonin concentrations from 10 pm and an earlier peak were observed in Estonian patients than in their age and sex matched controls (p<0.01). Starting from midnight, melatonin concentrations were significantly higher in the Estonian patients than in the Italian patients. No significant differences were observed for serum cortisol. Serum TNFalpha was higher (p<0.05) in Estonian patients than in their controls and was correlated with the melatonin levels. CONCLUSIONS: In a north European country (Estonia), the circadian rhythm of serum concentrations of melatonin and TNFalpha in patients with rheumatoid arthritis were significantly higher than in matched controls or in rheumatoid patients from a south Europe country (Italy).

Use of a peptide based enzyme immunoassay in diagnosis of Chlamydia trachomatis triggered reactive arthritis.

OBJECTIVE: To assess the presence of circulating IgA and IgG antibodies to Chlamydia trachomatis in sera of patients with reactive arthritis (ReA) and other arthritides. METHODS: A peptide based enzyme immunoassay (EIA) was used to study 132 patients divided into 5 groups: C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and rheumatoid arthritis (RA). Followup sera were available from 19 patients. RESULTS: An increased prevalence of C. trachomatis antibodies was observed in patients with ReA triggered by C. trachomatis; 18/23 (78%) had IgA and 19/23 (83%) had IgG antibodies. In patient groups with uroarthritis (n = 12), enteroarthritis (n = 56), oligoarthritis (n = 16), and RA (n = 25), C. trachomatis IgA/IgG antibodies were detected in 58%/75%, 27%/21%, 25%/31%, and 20%/32% of patients, respectively. Both the IgA and IgG antibodies were positive in 74%, 50%, 16%, 25%, and 12% of the patients with C. trachomatis triggered ReA, uroarthritis, enteroarthritis, oligoarthritis, and RA, respectively. Based on positivity of both isotypes the sensitivity of the assay was 74% and specificity 84%. In the followup sera, an association between circulating C. trachomatis-specific antibody concentrations and clinical disease outcome of the arthritis was seen in patients with culture-positive C. trachomatis triggered ReA. CONCLUSION: C. trachomatis species-specific peptide EIA correlates well with conventional diagnosis of primary C. trachomatis infection in patients with ReA. This assay may be a valuable contribution to the diagnosis of C. trachomatis triggered ReA.