Publications

In his clonal selection theory, Frank Macfarlane Burnet predicted that autoreactive lymphocytes are deleted to prevent autoimmunity. This and other principles of lymphocyte behavior outlined by Burnet guided many studies that lead to our current understanding of thymic selection. Thus, when the genetic mutation responsible for autoimmune polyglandular syndrome type 1 was mapped to the autoimmune regulator (AIRE) gene, and Aire was found to be highly expressed in thymic epithelium, studying the role of Aire in negative selection made sense in the context of modern models of thymic selection. We now know Aire is a transcription factor required for the expression of many tissue-specific antigens (TSAs) in the thymus. In the absence of functional Aire, human patients and mice develop multi-organ autoimmune disease because of a defect in thymic negative selection. In addition to its role in the thymus, recent work in our lab suggests that extrathymic Aire-expressing cells have an important role in the clonal deletion of autoreactive CD8+ T cells. In this review, we summarize the latest studies on thymic and peripheral Aire-expressing cells, as well as other TSA-expressing stromal cell populations in peripheral lymphoid organs. We also discuss theoretical differences in thymic and peripheral Aire function that warrant further studies.

BACKGROUND

Although inappropriate shocks are known to be an important consequence of implantable cardioverter-defibrillators (ICDs), the subjective experience of pain intensity perceived by those receiving inappropriate versus appropriate shocks has not previously been examined.

METHODS

One hundred ICD patients underwent a standardized interview by an investigator blinded to the clinical history. Patients with a previous ICD shock were asked to describe the intensity of the associated pain on a standard 0-10 scale (10 being the worst pain they had ever experienced). Medical charts were then examined for any history of inappropriate and/or appropriate ICD discharges.

RESULTS

Thirty-five of the 100 patients had a record of at least one ICD shock, and 17 had experienced at least one inappropriate shock. Those with a history of an inappropriate shock described a significantly higher median pain scale (9, interquartile range [IQR] 8-10) compared to those with a history of only appropriate shocks (median 4, IQR 2-8, P = 0.0011). In multivariable analysis, a history of an inappropriate shock was the only predictor statistically significantly associated with an increase in shock pain: the pain scale for those with inappropriate shocks was higher by 2.8 points on average after multivariable adjustment (95% confidence interval 0.29-5, P = 0.030). Eighteen patients had considered having their device deactivated, and a history of an inappropriate shock was the only factor independently associated with this consideration.

CONCLUSIONS

Compared to those who have received only appropriate shocks, inappropriate ICD shocks are associated with a recollection of greater pain and consideration of device inactivation.

OBJECTIVE

Disease activity and medication use can complicate pregnancies in patients with systemic lupus erythematosus (SLE). We therefore examined contraceptive counseling and use among women in the University of California, San Francisco Lupus Outcomes Study.

METHODS

In 2008, we queried participants regarding their pregnancy intentions, contraceptive use, and receipt of contraceptive counseling. Premenopausal women age <45 years who were sexually active with men were considered at risk of pregnancy. We compared self-reported rates of contraceptive counseling and use stratified by treatment with teratogenic medications and by history of thrombosis or antiphospholipid antibodies (aPL), using chi-square tests. We used logistic regression models to examine predictors of contraceptive counseling and use.

RESULTS

Among 206 women, 86 were at risk for unplanned pregnancy. Most (59%) had not received contraceptive counseling in the last year, 22% reported inconsistent contraceptive use, and 53% depended solely on barrier methods. Intrauterine device contraceptives (IUDs) were used by 13%. Women using potentially teratogenic medications were no more likely to have received contraceptive counseling, to have used contraception consistently, or to have used more effective contraceptives. A history of thrombosis or aPL did not account for low rates of hormonal methods. Four women with a history of thrombosis or aPL were using estrogen-containing contraceptives.

CONCLUSION

Most women at risk for unplanned pregnancy reported no contraceptive counseling in the past year, despite common use of potentially teratogenic medications. Many relied upon contraceptive methods with high failure rates; few used IUDs. Some were inappropriately using estrogen-containing contraceptives. These findings suggest the need to improve the provision of contraceptive services to women with SLE.