Bonnie L. Bermas

Sexual disparities in the incidence and course of SLE and RA

Systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) disproportionately affect females compared to males, with female to male prevalence ratios of 7-9:1 for SLE and 2-3:1 for RA. Interestingly, epidemiologic studies indicate that men that develop SLE may have more morbidity than women, but the same is not true for RA. Given the sex and age bias of SLE and RA, sex hormones may influence the pathogenesis of these diseases. However, the ways in which, and to what degree, sex hormones affect disease incidence and severity remain unclear and is the topic of ongoing research. Recent findings have implicated interactions between sex hormones, the immune system, genetic factors, and epigenetic modifications in influencing SLE and RA disease activity. This article reviews current hypotheses regarding the potential impact of sex hormones and genetics on disease pathogenesis, incidence, and severity of SLE and RA.

Expression of CD44 variant isoforms CD44v3 and CD44v6 is increased on T cells from patients with systemic lupus erythematosus and is correlated with disease activity

OBJECTIVE To quantify the expression of CD44 and variant isoforms CD44v3 and CD44v6 on T cells from patients with systemic lupus erythematosus (SLE), and to assess correlations of the level of expression of these molecules with disease manifestations. METHODS Information on clinical and demographic characteristics was collected, and blood samples were obtained from 72 patients with SLE and 32 healthy control subjects matched to the patients by sex, race, and age. Expression of CD44 and variants CD44v3 and v6 on T cell subsets was determined by flow cytometry, and Pearsons correlations of their expression levels with clinical variables, SLE Disease Activity Index (SLEDAI) scores, and presence of lupus nephritis were determined. Wilcoxons rank sum tests and conditional multivariable regression analyses were applied to identify differences in the expression of CD44 between patients with SLE and healthy controls. RESULTS Expression of CD44 was higher on CD4+ and CD8+ T cells from SLE patients compared with controls (P <or= 0.03). Expression of CD44v3 and CD44v6 was also higher on total T cells and CD4+ and CD8+ T cells from SLE patients compared with controls (P <or= 0.03). Cell surface levels of CD44v3 on total T cells, CD4+ T cells, and CD8+ T cells as well as cell surface expression of CD44v6 on total T cells and CD4+ T cells were correlated with the SLEDAI score (P < 0.05). The presence of lupus nephritis was associated with the expression of CD44v6 on total T cells, CD4+ T cells, and CD4-CD8- T cells (P < 0.05). Positivity for anti-double-stranded DNA antibodies was associated with the expression levels of CD44v6 on T cells (P < 0.05). CONCLUSION These results indicate that expression levels of CD44v3 and CD44v6 on T cells may represent useful biomarkers of SLE activity.

Proliferative responses to recall antigens are associated with pregnancy outcome in women with a history of recurrent spontaneous abortion.

Maternal tolerance of the fetal hemiallograft suggests that immunomodulation occurs during gestation. Therefore, recurrent spontaneous abortion (RSA) may represent a failure of the immune changes that maintain pregnancy. We hypothesized that fertile women but not women with RSA may lose their immune responses to recall antigens when pregnant. This phenomenon has been seen in immunosuppressed transplant recipients and is associated with graft survival. Therefore, we evaluated proliferative responses to recall antigens in four groups of women: group 1, nonpregnant fertile women with no history of pregnancy loss and at least one prior healthy pregnancy, n = 13; group 2, nonpregnant women with a history of three or more spontaneous abortions, n = 28; group 3, healthy pregnant women between 6 and 9 wk of gestation without a history of prior pregnancy loss, n = 15; and group 4, pregnant women between 6 and 9 wk of gestation, with a history of RSA, n = 22. Proliferative responses of peripheral blood leukocytes to the recall antigens influenza and tetanus, alloantigens, and phytohemagglutinin were determined prospectively. Positive responses (stimulation index > 3) to recall antigens (a response to either influenza or tetanus was considered positive) were as follows: group 1 (nonpregnant fertile women), 11/13 (85%); group 2 (nonpregnant RSA women), 24/28 (86%); group 3 (pregnant fertile women), 4/15 (27%) (P </= 0.007); and group 4 (pregnant RSA women), 13/22 (59%) (P = 0.032) [corrected]. In group 4, there was 100% fetal survival in the nine women who lost responsiveness to recall antigens; however, in the 13/22 patients who responded to recall antigens, 9/13 (69%) had a repeat spontaneous abortion. These findings suggest that immunosuppression, indirectly measured by proliferation to recall antigens, is necessary for early pregnancy maintenance. Furthermore, this approach may be useful for predicting pregnancy outcome for women with RSA and may provide a useful means for designing and monitoring therapies.

Development and initial validation of a self-assessed lupus organ damage instrument.

The Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI) is a validated instrument for assessing organ damage in systemic lupus erythematosus (SLE). Trained physicians must complete it, thus limiting utility where this is impossible.

Clinical manifestations and survival among adults with (SLE) according to age at diagnosis.

Objectives The objective of this paper is to determine the effect of clinical and laboratory manifestations, and medication prescribing, on survival according to patient age at diagnosis in a large academic systemic lupus erythematosus (SLE) cohort. Methods We identified SLE patients with a diagnosis at age ≥18, seen between 1970 through 2011, and with more than two visits to our lupus center. Data collection included SLE manifestations, serologies, other laboratory tests, medications, dates, and causes of death. We examined characteristics of those diagnosed before age 50 (adult onset) compared to those diagnosed at or after age 50 (late onset) using descriptive statistics. We used Kaplan-Meier curves with log rank tests to estimate five- and 10-year survival in age-stratified cohorts. Predictors of 10-year survival were assessed using Cox regression models, adjusted for calendar year, race/ethnicity, sex, lupus nephritis, and medication use. Results Of 928 SLE patients, the mean age at diagnosis was 35. Among the adult-onset group, there was significantly higher prevalence of malar rashes and lupus nephritis. Glucocorticoids, azathioprine, mycophenolate, and cyclophosphamide use were also more frequent in the adult-onset group compared to the late-onset group. Five-year survival rates were 99.5% and 94.9% and 10-year survival rates were 97.8% and 89.5%, among those diagnosed before and at or after age 50. In the entire cohort, increasing age at diagnosis, male sex, and black race were statistically significant predictors of reduced 10-year survival. Compared to those diagnosed before age 50, the late-onset group had a multivariable-adjusted hazard ratio for 10-year risk of death of 4.96 (95% CI 1.75–14.08). The most frequent cause of known death was a lupus manifestation, followed by cardiovascular disease and infection. Conclusions In our cohort, several demographic features, SLE manifestations, and medication prescribing differed between those with adult-onset and late-onset SLE. Ten-year survival rates were high for both groups, but relatively lower among late-onset patients. A lupus manifestation as the cause of death was more common among adult-onset compared with late-onset patients.

Patterns of medication use during pregnancy in rheumatoid arthritis

To characterize therapies prescribed during pregnancy to women with rheumatoid arthritis (RA).

The biology behind the new therapies for SLE.

Background:  Systemic lupus erythematosus (SLE) is a heterogenous disease with complex pathogenesis.

Marital satisfaction in couples with rheumatoid arthritis.

OBJECTIVE To understand correlates of marital satisfaction in persons with rheumatoid arthritis (RA) and their spouses. METHODS In a cross-sectional survey, 79 persons with RA and 78 spouses completed the Kansas Marital Satisfaction Scale, the revised Ways of Coping Questionnaire scales, and the Health Assessment Questionnaire. A series of linear regression analyses were then performed to investigate correlates of marital satisfaction for patients and spouses. RESULTS Seventy-six percent of patients were women. Mean patient age was 56.5 years (+/- 12.5 years), number of years married was 30.7 (+/- 13.5), and duration of RA was 14.2 years (+/- 9.0 years). Demographic features of spouses resembled those of patients. Patients and spouses were generally satisfied with their marriages. Linear regression analyses showed that lower marital satisfaction in patients was associated with higher education level (P < 0.01), patients greater use of escape into fantasy (P < 0.01), patients greater use of finding blame (P < 0.05), and spouses higher use of escape into fantasy (P < 0.001). Spouses less satisfied with their marriages were more likely to use passive acceptance (P < 0.05) and less likely to find blame (P < 0.05). Female spouses were less likely to be satisfied in their marriages (P < 0.01) than male spouses. CONCLUSIONS This study indicates that certain passive coping styles are associated with lower marital satisfaction in persons with RA and their spouses. More highly educated patients and female spouses are also less satisfied in their marriages. These cross-sectional correlations should not be regarded as causal and should be examined further in longitudinal studies.

Proceedings from the American College of Rheumatology Reproductive Health Summit: the management of fertility, pregnancy, and lactation in women with autoimmune and systemic inflammatory diseases.

Most autoimmune and systemic inflammatory diseases are more common in women than in men, including women of child-bearing age. Therefore, for many of our patients, family planning is an important clinical issue. The management of pregnancy in autoimmune diseases is complex, benefitting optimally from a multidisciplinary approach that takes into consideration: prepregnancy counseling; treatments received prior to, during, and after pregnancy; early recognition of both obstetric complications and medical complications relating to the underlying disease; prenatal fetal development; and postnatal management of the

Evaluation and management of systemic lupus erythematosus and rheumatoid arthritis during pregnancy

Women of childbearing age are at risk for developing systemic rheumatic diseases. Pregnancy can be challenging to manage in patients with rheumatic diseases for a variety of reasons including the impact of physiological and immunological changes of pregnancy on underlying disease activity, the varied presentation of rheumatic disease during pregnancy, and the limited treatment options. Previously, patients with rheumatic disease were often advised against pregnancy due to concerns of increased maternal and fetal morbidity and mortality. However, recent advancements in the understanding of the interaction between pregnancy and rheumatic disease have changed how we counsel patients. Patients with rheumatic disease can have successful pregnancy outcomes, particularly when a collaborative approach between the rheumatologist and obstetrician is applied. This review aims to discuss the effect of pregnancy on patients with the most common rheumatic diseases, the effect of these diseases on the pregnancy itself, and the management of these patients during pregnancy.