Synovial fluid OX40T lymphocytes of patients with rheumatoid arthritis display a Th2/Th0 polarization.

Rheumatoid arthritis (RA) is an autoimmune disease in which T-cell activation plays a pivotal role in the induction of articular damage. CD4+/OX40+ T cells accumulate in the synovial fluid (SF) of RA patients, which suggests that they are involved in the pathogenesis of the disease. In this study, we assessed the intracellular cytokine production of peripheral blood and SF CD4+ and CD4+/OX40+ T cells from RA patients in order to evaluate their role in this disorder. Our results show that SF CD4+ cells are predominantly interferon gamma (IFN-gamma)-positive and express a Th1-like cytokine pattern. In SF, significantly more CD4+/OX40+ T cells expressed interleukin-4 (IL-4) and IL4/IFN-gamma than IFN-gamma alone. Our data demonstrate that SF CD4+/OX40+ T cells express a Th2/Th0 cytokine profile, which suggests that they are involved in inflammatory responses in RA joints.

Anti-HLA antibodies in kidney transplanted patients.

Anti-human leukocyte antibodies (HLA) play a central role in graft survival, particularly in kidney transplantation. The presence of preformed donor specific anti-HLA antibodies is always excluded before transplantation by performing crossmatches using current and historic recipient serum samples. Several recent studies have observed a correlation between HLA antibodies and graft rejection. It has been suggested that these antibodies should be monitored routinely after kidney transplant to predict graft failure. Here in report the results of a study of on serum samples from 111 kidney transplant recipients that were monitored for anti-HLA antibodies using flow cytometry. Anti-HLA antibodies were only detected in four pre-immunized patients and showed the same HLA specificity that was present before the transplantation (in two cases against previous graft antigens). Furthermore, only two patients with functioning grafts developed anti-HLA antibodies, at 1 month and 1 year after the transplantation. However, they were not donor specific, but probably related to posttransplant transfusions. In our study, none of the patients who suffered an adverse event during the first year (including two with histologically documented acute rejection) developed anti-HLA antibodies. These results are probably related to the use of mycophenolate mofetil, which may reduce the incidence of HLA antibodies. We cannot exclude the possibility that antibodies produced by some patients may not be detectable because they are attached to the graft.

Infectious complications in the renal transplant recipient.

The aim of this study was to estimate the incidence of infectious diseases in a group of patients who underwent kidney transplantation from January 1, 2004 to September 30, 2004, including 121 operations, with 119 from cadaveric and 2 from living donors. The protocol sought herpes viruses (CMV, VZV, and EBV), hepatitis viruses, human immunodeficiency virus, T. gondii, M. tubercolosis, and T. pallidum. Therapy for CMV was used both as prophylaxis in immunoglobulin (Ig)G-negative recipients from IgG-positive donors and preemptive therapy, that is, before the appearance of clinical symptoms, but after viremia reached borderline levels. For VZV infections, the treatment started after the appearance of papulo-vesicular cutaneous eruptions and antibody positivity. The treatment for pneumonia consisted of empirical therapy after radiography; for pyelonephritis, antibiotic therapy was based on the results of kidney echography, blood culture, and urine culture. Infectious complications appeared in 25 patients (20.7%), 3 of the which were polymicrobic: 12 CMV infections, 9 VZV infections, 3 pneumoniae, 4 pyelonephritis, and 1 salmonellosis. The most frequent infection was CMV, which occurred in the first 3 months after transplantation in 9 of 12 cases. This study showed that a knowledge of infection prevalence can help the physician to establish a more specific, efficacious antimicrobial therapy, despite the laboratory response not being available in a short time.

Urologic complications in kidney transplantation.

Urologic complications in kidney transplantation have an incidence ranging from 3% to 20%, representing an important cause of organ loss. From January 2001 to September 2004, 123 renal transplantations were performed using an immunosuppressive protocol including basiliximab, mycophenolate mofetil, calcineurin inhibitors, and steroids. The surgical technique was vascular anastomoses to external iliac vessels, and ureteral anastomosis according to Lich Gregoire technique using a JJ ureteral stent. We report 5 renal complications (4.2%) and 4 extrarenal complications (3.5%), the majority of which required corrective surgery. The surgical strategy uses the clinical condition of the donor and the recipient; the anatomic anomalies of the graft, and a reduced cold ischemia time. Moreover, a reduction in acute rejection episodes and immediate renal function has been fundamental to reduce urologic complications. In fact, the main cause of urologic complications is ureteral ischemia, linked both to backtable surgery and to rejection episodes. Another important factor in the reduction of early urologic complications has been the routine use of a JJ stent, which allowed us a conservative approach in this setting.

Cutaneous manifestations in Italian kidney transplant recipients.

Several cutaneous disorders may occur in organ transplant recipients. We examined the incidence and the clinical spectrum of cutaneous manifestations among kidney transplant recipients. One hundred nine patients (70 males and 39 females), aged 19 to 69 years (mean: 42.5 years), were consecutively examined as outpatients between June 2000 and August 2004. The mean interval after kidney transplantation was 61 months (range: 2 to 120 months). The immunosuppressive regimen consisted of combinations including cyclosporine, systemic corticosteroids, azathioprine, tacrolimus, mycophenolate mofetil, antivirals, and antibiotics. Ninety-one cutaneous manifestations were identified in 60 of 109 (55.0%) kidney transplant patients over a 4-year period. Sixteen (17.5%) cutaneous viral infections identified in 11 patients (10.0%) included verruca vulgaris (n = 9), herpes zoster (n = 5) and herpes simplex (n = 2). Thirteen (11.9%) patients showed 19 (20.8%) superficial fungal infections, consisting of dermatophytosis (n = 6), onycomycosis (n = 6), pityriasis versicolor (n = 5) and mucocutaneous candidiasis (n = 2). Twenty (22%) nonmelanoma skin cancers were identified in seven (6.4%) patients, six basal cell carcinomas (BCC) in four patients, two squamous cell carcinomas (SCC) in two patients, and 11 BCCs in addition to one SCC in one patient. Twenty-six (23.8%) patients developed 32 (35.4%) drug-related manifestations, including acneiform eruption (n = 14), gingival hypertrophy (n = 6), hypertrichosis (n = 6), ecchymosis (n = 3), and plantar hyperkeratosis (n = 3). In addition, psoriasis and seborrheic dermatitis, which had been diagnosed before kidney transplantation, were observed in five and three patients, respectively. Our results emphasize the importance of dermatologic examinations and monitoring kidney transplant recipients to obtain an early diagnosis and treatment of cutaneous manifestations.

Malignancies after kidney transplantation.

The most effective treatment of end-stage renal disease is renal transplantation; its superiority to prolong the longevity of patients is well established. Patient and graft survivals have improved with more potent immunosuppression but this advance has been associated with an increased incidence of cancer. The aim of this study was to assess the prevalence of cancer among 265 kidney transplant recipients engrafted between 1968 and October 2004. The overall prevalence of de novo malignancies was 3%. The mean age at diagnosis was 53.3 years (range, 28-63 years) and the duration of the transplant was 11.6 years (range, 0.3-33 years). One patient among 127 (0.8%) who had a history of less than 3 years under immunosuppression, developed a posttransplantation lymphoproliferative disorder (PTLD). Among the 138 patients who had more than 3 years immunosuppression, 7 (5%) developed neoplasms of vulva, colon, native kidneys, prostatic gland, and ovary. One patient was affected by de novo carcinoma in the transplanted kidney. Compared with other published studies, our early cancer prevalence is low, possibly due to a careful history before grafting, good HLA matching, and abstinence from anti-T-cell therapy for treatment of acute rejection episodes. The low level of immunosuppression may account for the low prevalence of neoplasia. The risk of developing a malignancy increases with long-term immunosuppression, comparable with most reports.

Effects of interferon beta, cyclophosphamide and azathioprine on cytokine profile in patients with multiple sclerosis.

We assessed the in vitro effects of interferon beta-1b (IFNbeta-1b), cyclophosphamide (CY), and azathioprine (AZA) alone and of the combination of IFNbeta-1b with CY or AZA on the production of Th1 and Th2 cytokines in 10 patients with multiple sclerosis. Cytokine levels were determined at baseline and after stimulation with IFNbeta-1b, CY, and AZA alone or with the combination of IFNbeta-1b with CY or AZA. The combination of IFNbeta-1b with CY resulted in a statistically significant decrease in the production of interleukin-2 (IL-2) (P=0.003) and tumor necrosis factor alpha (TNF-alpha) (P=0.03). An additive effect on the production of interferon gamma (IFN-gamma) (P=0.2) and interleukin-10 (IL-10) (P=0.6), and a positive interaction on the production of interleukin-4 (IL-4) (P=0.08) were observed although the findings were not statistically significant. The combination of IFNbeta-1b with AZA resulted in a significant negative effect on the production of IL-2 (P=0.006), whereas TNF-alpha (P=0.02), IFN-gamma (P=0.03), IL-4 (P=0.2), and IL-10 (P=0.3) were not statistically impacted. Our data show that CY was able to improve the effects of IFNbeta-1b on the ratio of Th1/Th2 cytokines.

T lymphocytes in the synovial fluid of patients with active rheumatoid arthritis display CD134-OX40 surface antigen.

OBJECTIVE: To assess the percentage of T lymphocytes, bearing CD134, a member of the TNF receptor superfamily, primarily found on autoreactive CD4+ T cells in the peripheral blood (PB) and synovial fluid (SF) of rheumatoid arthritis (RA) patients. METHODS: The surface expression of CD134 on SF and PB mononuclear cells was performed by flow cytometry in 25 RA patients and correlated to the disease activity. RESULTS: CD134 expression on CD3+, CD4+, CD8+ and CD25+ cells was higher in SF than in PB of RA patients (P < 0.001). No differences were observed in the percentage of CD134+/CD4+ T lymphocytes in the PB of RA patients and controls. Patients with active RA had significantly higher percentage of CD3+/CD134+, CD4+/CD 134+, CD8+/CD134+ and CD25+/CD 134+ than those with inactive disease. CONCLUSION: These findings suggest that CD134+ T cells are involved in the immunopathological process of RA synovitis, maybe mirroring some other autoimmune disease in which autoreactive T cell infiltrating the target tissues largely coexpress CD134.