Jerald M. Zakem

Circulating CXCR5+CD4+helper T cells in systemic lupus erythematosus patients share phenotypic properties with germinal center follicular helper T cells and promote antibody production.

Objective Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies. Recently, a specific highly activated T helper cell subset, follicular helper T (Tfh) cell, has emerged as a key immunoregulator of germinal center (GC) formation and high-affinity antibody production. To identify the pathophysiological role of Tfh cells in SLE patients, we compared the phenotypic and functional properties of circulating Tfh-like cells in lupus patients to GC-Tfh cells, and correlated the percentage of Tfh-like cells with autoantibody production and SLE disease activity. Methods Peripheral blood was collected from 29 lupus patients and 25 healthy controls. Tonsils were obtained surgically from non-SLE controls and used as a source of GC-Tfh cells. Tfh cells were defined by their signature surface markers (CXCR5, ICOS, CD57, PD-1 and BTLA) via flow cytometry. IL-21 expression levels from Tfh cells were measured by real-time PCR and intracellular staining. The function of Tfh cells was carried out by co-culture of Tfh cells and autologous B cells in vitro. IgG in the culture supernatant was detected by ELISA. Results The frequency of circulating Tfh-like cells was significantly increased in SLE patients compared to healthy controls (p < 0.05). The Tfh-like cells not only display similar phenotypes and signature cytokines with GC-Tfh cells, but also are capable of driving B cells to differentiate into IgG-secreting plasma cells in vitro. In addition, the frequency of Tfh-like cells correlated positively with the percentage of circulating plasmablasts, levels of serum anti-dsDNA antibodies and ANA. Conclusion The accumulated circulating Tfh-like cells in lupus patients share phenotypic and functional properties with GC-Tfh cells. Tfh-like cells may serve as perpetuators in the pathogenesis of SLE by enhancing the self-reactive B cell clones to further differentiate into auto antibody-producing plasmablasts, and ultimately cause autoimmunity.

Tumor necrosis factor-alpha antagonist-induced sarcoidosis.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Tumor necrosis factor (TNF)-alpha is an important player in granuloma formation, and recent clinical trials have investigated the efficacy of TNF-alpha inhibitors in sarcoidosis. Paradoxically, there are several case reports in the medical literature describing the development of sarcoidosis in patients treated with TNF-alpha inhibitors. We describe 3 cases of TNF-alpha antagonist-induced sarcoidosis: 1 case of pulmonary, ocular and cutaneous sarcoidosis developing in a patient receiving infliximab for erosive rheumatoid arthritis, 1 case of etanercept-induced sarcoidosis in a patient with seronegative rheumatoid arthritis, and 1 case of sarcoidosis developing in a patient receiving etanercept for erosive rheumatoid arthritis. We also provide a brief discussion on the role of TNF alpha in granuloma formation and implications in the use of TNF-alpha antagonists in autoimmune disease.

Implementation of a Mandatory Rheumatology Osteoporosis Consultation in Patients With Low-Impact Hip Fracture

Background:Osteoporosis remains an underdiagnosed and undertreated major health problem. The current treatment rate for patients who have experienced at least 1 osteoporotic fracture is 20%–25%. Therefore, the Rheumatology and Internal Medicine Departments of Ochsner Clinic Foundation New Orleans implemented a mandatory rheumatology osteoporosis consult as part of preprinted admission orders for all patients after hip fracture surgery on the Internal Medicine service. Methods:We conducted a retrospective study of 78 patients admitted with a low-impact hip fracture between June 2004 and July 2005. These patients were seen by the rheumatology service in the hospital after hip fracture repair (exposed group). Osteoporosis evaluation was performed based on an interview questionnaire. Seventy-eight age-matched patients previously admitted for low-intensity or low-impact hip fracture in 2002–2003 but not exposed to the mandatory rheumatology consult served as our comparison group. Pearson χ2 test was used for statistical analysis. Results:Mean patient age was 80 years. Of the 78 unexposed patients, 17 (22%) were on treatment (calcium, vitamin D, hormones or antiresorptive agents) before the hip fracture, and 18 (23%) were on treatment after fracture repair. Of the 78 patients exposed to the compulsory rheumatology consultation, 34 (44%) patients were receiving osteoporosis treatment before hip fracture and 75 (96%) patients were receiving treatment after fracture repair. Of the patients not treated before hip fracture repair, there was a significant increase in the percent treated for those patients exposed to the rheumatology consult versus those not exposed (97.6% vs. 2.4%, respectively, P < 0.0001). Conclusions:In our institution, we were successful in identifying and initiating appropriate therapy for osteoporosis patients through an automatic rheumatology osteoporosis consultation after hip fracture. The implementation of a mandatory osteoporosis consult resulted in a statistically significant increase in treatment of the exposed group compared with the unexposed group.

Adoption Of New Electronic Medical Records May Inhibit Documentation Of Physician Quality Reporting System

SUPPLEMENTSex Bias In Autoimmune Diseases : Increased Risk Of 47,XXX In Systemic Lupus Erythematosus (SLE) and Sjogrens Syndrome (SS) Supports The Gene Dose HypothesisBackground/Purpose: Human FoxP3+ Th-cells are heterogeneous in function and include not only suppressive cells (TRegs) but also nonsuppressive cells that abundantly secrete proinflammatory cytokines. We have previously shown that FoxP3+ Th-cells were increased in GPA-patients during remission as compared to healthy controls (HCs). In this group of patients, however, we observed a defective suppressor function of TRegs, and an increase in the percentage of Th-17 cells. These observations make it tempting to investigate whether increased FoxP3+ Th-cells in GPA-patients are attributed to an increase in the cytokine-secreting non-suppressive FoxP3+Th-cells. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from 46 GPA-patients in remission and from 22 age- and sex-matched HCs. Expression of CD4, CD45RO, and FoxP3 were determined by flow cytometric analysis. The expression levels of FoxP3 and CD45RO were used for distinction between activated suppressor TRegs (FoxP3HighCD45RO+; ASTReg), resting suppressor TRegs (FoxP3LowCD45RO-; RSTReg), and cytokine-secreting non-suppressor TRegs (FoxP3LowCD45RO+; NONTReg) cells. Intracellular expression of IFNg, IL-17, and IL-21 were determined in the various FoxP3+ Th-cell subsets after in vitro activation of PBMCs by PMA and Ca-Ionophore. Results: A significant increase in the frequency of NONTReg cells was observed in GPA-patients as compared with HCs, whereas no differences were detected in RSTReg- and ASTReg cells between GPA-patients and HCs. The distribution of RSTReg- and NONTReg cells did not differ between ANCA-negative and ANCA-positive patients, whereas lower percentages of ASTReg cells were observed in ANCA-positive patients as compared to ANCA-negative patients and HCs. Importantly, a significant increase in the percentage of IL-17+ and IL-21+ cells was seen within the NONTRegcells from ANCA-positive patients (n= 9) when compared to ANCA-negative (n= 10) and HCs (n= 12), whereas no differences were found between ANCA-negative and HCs. Conclusion: Increased FoxP3 expression in Th-cells from GPA-patients is related to an increase in a subset of non-suppressive Th-cells. Increased production of IL-17 and IL-21 cytokines, in NONTReg cells from ANCApositive patients points towards FoxP3+ effector cells and decrease in suppressive TReg cells in relation to ANCA production.Complex Functional Effects Within The HLA Contribute To Sjogrens Syndrome Pathogenesis and May Influence Both Transcriptional Regulation and Peptide Binding