Francisca Sabugo

Effect of interleukin‐6 receptor blockade on the balance between regulatory T cells and T helper type 17 cells in rheumatoid arthritis patients

A new paradigm has emerged relating the pathogenesis of rheumatoid arthritis (RA), focused on the balance between T helper type 17 cells and regulatory T cells (Tregs). In humans, both subpopulations depend on transforming growth factor (TGF)‐β for their induction, but in the presence of inflammatory cytokines, such as interleukin (IL)‐6, the generation of Th17 is favoured. Tocilizumab is a therapeutic antibody targeting the IL‐6 receptor (IL‐6R), which has demonstrated encouraging results in RA. The aim of this study was to evaluate the effect of tocilizumab on Th1 cells, Th17 cells, IL‐17 and interferon (IFN)‐γ double secretors Th17/Th1 cells, and Tregs in RA patients. Eight RA patients received tocilizumab monthly for 24 weeks and blood samples were obtained every 8 weeks to study T cell populations by flow cytometry. The frequency of Th17 cells, Th1 cells and Th17/Th1 cells was evaluated in peripheral blood mononuclear cells (PBMCs) activated in vitro with a polyclonal stimulus. Tregs were identified by their expression of forkhead box protein 3 (FoxP3) and CD25 by direct staining of PBMCs. Although no changes were detected in the frequency of Th1 or Th17 cells, the percentages of peripheral Tregs increased after therapy. In addition, the infrequent Th17/Th1 subpopulation showed a significant increment in tocilizumab‐treated patients. In conclusion, tocilizumab was able to skew the balance between Th17 cells and Tregs towards a more protective status, which may contribute to the clinical improvement observed in RA patients.

B cells from rheumatoid arthritis patients show important alterations in the expression of CD86 and FcγRIIb, which are modulated by anti-tumor necrosis factor therapy

IntroductionSeveral molecules help preserve peripheral B cell tolerance, but when altered, they may predispose to autoimmunity. This work studied the expression of the costimulatory molecule CD86 and the inhibitory receptor for IgG immune complexes FcγRIIb (CD32b), on B cells from rheumatoid arthritis (RA) patients, and the influence of anti-tumor necrosis factor (TNF) therapy.MethodsPeripheral B cells from 18 RA patients and 13 healthy donors were characterized using flow cytometry. Eleven patients who underwent a six-month adalimumab therapy were further assessed for phenotypic changes on their B cells.ResultsRA patients exhibited a high percentage of naïve and memory B cells expressing CD86. In contrast, expression of FcγRIIb was significantly reduced on RA memory B cells and plasmablasts as compared to healthy donors, probably due to downregulation of this receptor when differentiating from naïve to memory cells. These alterations on FcγRIIb were associated with high levels of anti-citrullinated vimentin autoantibodies. In addition, treatment with adalimumab normalized the expression of CD86 on memory B cells and reduced the expression of FcγRIIb, mainly on naïve B cells.ConclusionsOur findings show that peripheral B cells from RA patients have an altered expression of key molecules, such as CD86 and FcγRIIb. Because this latter receptor is required for feedback inhibition, a deficient expression might contribute to humoral autoimmune responses. Furthermore, these molecules are likely to be influenced by inflammatory factors, since they were modulated by TNF inhibition.

Comparison of the Clinical Efficacy of Two Different Immunosuppressive Regimens in Patients with Chronic Vogt-Koyanagi-Harada Disease

Purpose: To prospectively compare 2 immunosupressive regimens in patients with active Vogt-Koyanagi-Harada disease in spite of systemic glucocorticoid treatment. Methods: Forty-four patients were diagnosed between 1998 and 2005. Twenty-one developed chronic intraocular inflammation in spite of glucocorticoid treatment and were randomized to receive either prednisone and azathioprine (AZA) (n = 12) or prednisone and cyclosporine (CyA) (n = 9). Results: In the AZA group Tyndall score decreased from 1.21 ± 1.10 to 0.29 ± 0.62 (p < .01), and visual acuity (LogMAR) improved from 0.32 ± 0.35 to 0.09 ± 0.16 (p < .001). In the CyA group Tyndall score decreased from 1.67 ± 1.08 to 0.16 ± 0.51 (p < .001), and visual acuity improved from 0.41 ± 0.40 to 0.25 ± 0.42 (p < .001). Patients in the AZA group needed a significantly higher average prednisone dose and total cumulative dose than those in the CyA group, p < .01 for each comparison. Conclusions: Both regimens showed a good clinical efficacy, but CyA seems to be a better glucocorticoid-sparing agent than AZA.

Infliximab can induce a prolonged clinical remission and a decrease in thyroid hormonal requirements in a patient with SAPHO syndrome and hypothyroidism

SAPHO syndrome is a rare entity that compromises the skeletal system (arthritis–osteitis) and is associated with various dermatological conditions such as palmoplantaris pustulosis (PPP) and acne. We present the case of a 39-year-old man with invalidating arthritis derived from a SAPHO syndrome and hypothyroidism (after radioiodine treatment for a Graves’ disease). Due to the severity and refractoriness of his disease, we decided to use infliximab. He showed a prompt and prolonged response of his joint and cutaneous manifestations after three doses of a tumor necrosis factor alpha (TNF-α) blocker. Interestingly, he also decreased his levothyroxine requirements after TNF-α blockade therapy.

Enfermedad de Behçet en Chile: Análisis clínico de 44 casos

12 years. According to BDCJ criteria, 13 patients had complete BD, 24 hadincomplete BD and 7 had a suspected BD. Thirty two patients fulfilled the ISG criteria. Forty twopatients (95%) had oral ulcers, 33 (75%) had genital ulcers and 29 (66%) hadophthalmological involvement. Eleven and three patients had symptoms of central andperipheral nervous system involvement, respectively. No gender differences were detected.

Acute herpes simplex virus 1 pneumonitis in a patient with systemic lupus erythematosus.

A woman with severe and longstanding systemic lupus erythematosus presented with a 1-week history of fever up to 38°C and pain in her right flank. Computed tomography scan of the chest revealed interstitial infiltrates and multiple nodules. Bronchoalveolar lavage did not show any inflammatory cells. Gram stain and cultures for aerobic and anaerobic bacteria, fungi, and Nocardia; acid-fast staining; polymerase chain reaction for tuberculosis, cytomegalovirus, herpesvirus 6, and parvovirus B19; and IF staining for pneumocystic and Legionella antigen were all negative. Transbronchial biopsy was nondiagnostic. Open lung biopsy with polymerase chain reaction and immunohistochemistry analyses revealed herpes simplex virus 1 infection. Acyclovir therapy was initiated and was followed by significant improvement. Herpes simplex virus 1 infection (although unusual) should be considered in patients with systemic lupus erythematosus with an atypical clinical presentation.

Aortitis, causas infrecuentes en Reumatología: presentación de casos

Aortitis is a nonspecific term that describes an inflammation of the aortic wall caused by inflammatory, infectious, paraneoplastic and idiopathic diseases. The symptoms are variable and nonspecific; therefore a high level of clinical suspicion is required to diagnose it. It is often an incidental finding while looking for other diagnoses and it is confirmed mainly through imaging studies. We report three cases of aortitis: A 29-year-old woman presenting with alopecia, oral and nasal ulcers and positive antinuclear antibodies. A CAT scan showed a segmental thickening of thoracic aorta, with dilated and stenotic areas. She was successfully treated with steroids, hydroxychloroquine, cyclophosphamide and azathioprine. A 41-year-old male presenting with dorsal pain and cough. The CAT scan showed an extra-intimal thickening of the descending aorta and stenosis of the celiac artery. The final diagnosis was a polyangiitis and was treated with steroids, cyclophosphamide and azathioprine. A 28-year-old woman presenting with pain in the left upper abdomen. Imaging studies showed a thickening of the aortic arch and subclavian artery. The final diagnosis was sarcoidosis and the patient was treated with prednisone.

Illness Experiences in Women with Oral Dryness as a Result of Sjögren's Syndrome: The Patient Point of View

BACKGROUND Sjögrens syndrome and the associated dryness can have multiple consequences. The aim of the present qualitative study was to give an in-depth account of the life experiences of women with primary Sjögrens syndrome (pSS) and health-related behaviours, and to summarize these experiences in an integrated model. METHODS Twelve women diagnosed with pSS who regularly attended the Hospital of the University of Chile participated in detailed interviews. The data were analysed using qualitative methods based on the principles of grounded theory. RESULTS Selective coding identified three categories: illness experience, social interaction and psychological response. An integrated model was developed connecting these dynamic aspects and suggesting how they could lead to a life cycle crisis in cases of maladjustment. We found that problem-solving strategies, reconstruction of identity, acceptance and a social support may prevent this life cycle crisis. DISCUSSION Xerostomia and other consequences of pSS can have a profound influence on daily life. However, the severity of the consequences depends on individual experiences with the illness, social influences and the psychological responses of the patient. Physicians, dentists and other healthcare professionals can help the patient by listening to their problems and exploring solutions based on a psychological approach.