Relationships between serum 17 ß-oestradiol and anticardiolipin antibody concentrations in female patients with rheumatoid arthritis

B. Seriolo, M. Cutolo, A. Garnero and S. Accardo

Division of Rheumatology, Department of Internal Medicine, University of Genova, Viale Benedetto XV, no. 6, 16132 Genova, Italy

Correspondence to: B. Seriolo, Via Guerrazzi, no. 14-2, 16146 Genova, Italy.

SIR, We read with great interest the article by Rood et al. [1] concerning the effect of female sex hormone levels at the onset of systemic lupus erythematosus (SLE) on the survival of these patients.

The authors report that a significantly higher mortality risk is observed in patients who have developed SLE during the reproductive years than in those who have developed the disease during the non-reproductive years.

Recent reports have confirmed an increased mortality in patients with rheumatoid arthritis (RA) when compared with the general population, with a particularly increased incidence in the rates of deaths due to cardiovascular diseases [2, 3].

The presence of antiphospholipid antibodies, such as anticardiolipin (aCL) antibodies and lupus anticoagulant (LAC), is associated with several autoimmune disorders, including antiphospholipid syndrome and SLE. The positivity of aCL antibodies in patients affected by autoimmune disorders correlates strongly with the concomitant appearance of thromboembolic complications such as peripheral vessel diseases, and cerebral and myocardial infarction [4].

Previous reports have shown increased concentrations of aCL antibodies in patients affected by RA, with an increased risk of different vascular complications, including arterial or venous thrombosis [5]. On the other hand, evidence suggests that physiological levels of oestrogens stimulate, while male hormones reduce, the immune response [6].

In the light of these observations, we would like to introduce here our experience concerning the relationships between serum levels of oestrogens and the presence of aCL antibodies in female patients with RA.

We evaluated serum concentrations of 17 ß-oestradiol in 104 female patients (mean±S.D. age 58±9 yr) fulfilling the 1987 American Rheumatism Association criteria for adult RA. The duration of the disease was 7.6±5.1 months (range 2–18 months). All the patients were tested for aCL antibodies at least three times during a 6 month period of observation and measured by ELISA as previously described [7]. Therefore, RA patients were grouped as aCL antibody positive (aCL+, n=21, 20%) and as aCL antibody negative (aCL-, n=83, 80%), depending on the presence of aCL antibodies. None of the patients had ever been treated with corticosteroids or the oral contraceptive pill. All patients analysed showed a normal variation of gonadal hormone and gonadotrophin concentrations during the menstrual cycle. 17 ß-oestradiol levels were measured by a solid-phase, chemiluminescent enzyme immunoassay (Diagnostic System Laboratories Inc., Webster, TX, USA) on whole sera stored at -20°C and obtained during the first 10 days of the menstrual cycle. The disease activity was evaluated by laboratory parameters such as the erythrocyte sedimentation rate (ESR), serum protein electrophoresis, C-reactive protein (CRP) and fibrinogen levels, as well as platelet count, obtained by routine methods. An age-matched control group of 62 female subjects affected by secondary osteoarthritis was used to obtain reference values for sex hormones. Statistical analysis was performed by Student's unpaired t-test and by Pearson's product–moment correlation coefficients, and tested for two-tailed probability values.

The combined group of patients with RA was found to have higher 17 ß-oestradiol levels compared with controls, but the difference was not statistically significant (mean±S.E.M. 34.9±3.1 vs 25.7±4.7 pg/ml, respectively). However, higher 17 ß-oestradiol levels were observed in aCL antibody-positive RA patients than in aCL antibody-negative RA patients (55.1± 12.3 vs 29.8±3.1 pg/ml, respectively; P=0.01). Furthermore, when the patients with RA were grouped depending on their pre- or post-menopausal status, significantly higher 17 ß-oestradiol levels were found in pre-menopausal patients with RA and aCL antibody positivity when compared with pre-menopausal patients with RA and aCL antibody negativity (see Table 1Go).


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TABLE 1.  RA patient and control characteristics. Values are expressed as the mean ± S.E.M.
 
Significant correlations between 17 ß-oestradiol levels and ESR (r=0.75, P=0.01), CRP (r=0.54, P=0.05) as well as fibrinogen (r=0.62, P=0.02) concentrations were found in aCL antibody-positive pre-menopausal patients.

Generally, our findings showing an association between the high levels of oestrogens and aCL antibody positivity in RA patients seem concordant with the observations of Rood et al. [1].

In conclusion, these results might suggest that persistent high 17 ß-oestradiol levels, observed at least in pre-menopausal patients with RA, may predispose to a more efficient immune response, including the enhanced expression of aCL antibodies. This correlation between 17 ß-oestradiol levels and aCL antibodies might contribute to the higher mortality risk of female patients during the reproductive years.

References

  1.  Rood MJ, Van Der Velde EA, Ten Cate R, Breedveld FC, Huizinga TWJ. Female sex hormones at the onset of systemic lupus erythematosus affect survival. Br J Rheumatol 1998;37:1008–10.[ISI][Medline]
  2.  Wolfe F, Mitchell DM, Sibley JT, Fries JF, Block DA, Williams CA et al. The mortality of rheumatoid arthritis. Arthritis Rheum 1994;37:481–94.[ISI][Medline]
  3.  Myllykangas-Luosujärvi R, Aho K, Kautiainen H, Isomäki H. Cardiovascular mortality in women with rheumatoid arthritis. J Rheumatol 1995;22:1065–7.[ISI][Medline]
  4.  Hughes GRV. The antiphospholipid syndrome. Ten years on. Lancet 1993;342:341–4.[ISI][Medline]
  5.  Seriolo B, Accardo S, Fasciolo D, Sulli A, Bertolini S, Cutolo M. Lipoprotein (a) and anticardiolipin antibodies as risk factors for vascular disease in rheumatoid arthritis. Thromb Haemostasis 1995;74:799–800.[ISI][Medline]
  6.  Cutolo M, Sulli A, Seriolo B, Masi MT. Estrogens, the immune response and autoimmunity. Clin Exp Rheumatol 1995;13:217–26.[ISI][Medline]
  7.  Seriolo B, Accardo S, Fasciolo D, Bertolini S, Cutolo M. Lipoprotein, anticardiolipin antibodies and thrombotic events in rheumatoid arthritis. Clin Exp Rheumatol 1996;14:593–9.[ISI][Medline]
Accepted 14 May 1999





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