Juergen Brunner

The expanded double negative T cell populations of a patient with ALPS are not clonally related to CD4+ or to CD8+ T cells

The autoimmune lymphoproliferative syndrome (ALPS) is characterized by non-malignant lymphoproliferation and signs of autoimmunity. A hallmark of ALPS are high amounts of circulating CD3+/CD4 − /CD8 − double negative T-lymphocytes (DN T cells). The origin of these cells remains elusive. To investigate the relationships of DN T cells and the single positive T cell populations (CD4+ and CD8+), we analyzed by spectratyping the complementarity determining regions 3 (CDR3) of the T cell receptors in sorted “single positive” (CD4+, CD8+) and DN T cells in a patient with ALPS type 1a. We observed signs for clonal expansion in all three T cell subpopulations. Strong and weak clonal expansions were to be seen in 16 and 14 for DN, 6 and 12 for CD8+, and 1 and 5 for CD4 + T cells, respectively. Most importantly, 24 out of 30 aberrant peaks in the spectratype histograms of the DN T cells where unique for this population and were not to be detected in the histograms of the single positive T cells. In contrast to published data, we conclude that expanded DN T cell populations in ALPS are not generally derived from expanded CD3+/CD4+ or CD3+/CD8+ populations.

Interleukin 1 blockade with canacinumab for hyperimmunoglobulin D and periodic fever syndrome.

Hyperimmunoglobulinemia D and periodic fever syndrome (HIDS; MIM# 260920) is a rare autosomal recessive autoinflammatory condition caused by mutations in the MVK gene, which encodes for mevalonate kinase. There is no standard treatment for HIDS.

The turnover of synovial T cells is higher than in T cells in the peripheral blood in persistent oligoarticular juvenile idiopathic arthritis

Juvenile idiopathic arthritis (JIA) summarizes a group of inflammatory diseases of childhood. The etiology remains still unclear. In JIA, T cells have been demonstrated to play key roles in the pathogenesis. T-cell proliferation in JIA may be different in the peripheral blood (PB) and the synovial fluid (SF). The aim of this study is to demonstrate the turnover of T cells in the PB and SF of patients with persistent oligoarticular JIA (oJIA) compared to controls. Matched pairs of samples were investigated derived from PB and SF of nine patients with persistent oJIA. The cells from PB and SF were determined by flow cytometry. The majority of the PBMC and IAMC were in phase G0/G1, with fewer than 1% in S phase. In the SF, the percentage of cells in the S phase are higher than in the PB. The percentage of cells in the S phase in SF are equal to the result in the control group. In conclusion, the turnover of synovial T cells in persistent oJIA is higher than in the PB.

SAT0257 Update on The Juvenile Systemic Sclerosis Inception Cohort Project. Characteristics of The First 74 Patients at First Assessment

Background Juvenile systemic sclerosis (jSSc) is an orphan autoimmune disease. Currently just retrospective data exist regarding evolvement of organ involvement. In the retrospective studies assessment of the organ involvement is not standardized. Our project is the first one, where prospectively and with a standardized assessment data of jSSc patients are collected. Objectives to learn about the characteristics and evolvement of jSSc Methods Patients with jSSc were recruited worldwide and were prospectively assessed, using the proposed standardized patient assessment protocol. Results 26 centers from 17 countries applied to participate on the project. The assent and consent forms were translated into the local native languages. Up till now 74 patients were enrolled. Sixty (81%) of the 74 patients were female. The mean age of the onset of Raynaud symptomatic was 9.2 years (0.2 – 15.9). The mean age at the onset of the non-Raynaud symptomatic were 9,7 years (0.3 -15.9). 56 (76%) of the 74 have diffuse subtype, 10 (14%) of them have an overlap symptomatic. At the time of the inclusion the mean modified Rodnan Skin Score was 16.0. ANA positive were 55/71 (77%), 24/70 (34%) of them were anti-Scl 70 positive and 3/42 (7%) was anticentromere positive. 43/74 (58%) had already capillary changes and 36/72 (50%) inactive ulcerations, 13/72 (18%) had active ulceration at the time of the inclusion. 38/74 (51%) had cardiopulmonary involvement, 19/38 (50%) of had signs of interstitial lung disease on imaging, 18/42 (43%) had FVC <80% and 12/21 (57%) had DLCO <80%. 6/38 (16%) patients had pulmonary hypertension. 5/74 (7%) had renal involvement. 26/74 (35%) had gastrointestinal involvement, and 23/26 (88%) of them esophageal involvement. 46/73 (63%) had musculoskeletal involvement. 2/74 (3%) showed neurologic involvement. The mean CHAQ score was 0.4 (0–2.5). Patient global disease activity on VAS (0–100) was 44.9 and disease damage 41.6. Physician global of disease activity on VAS (0–100) was 39.7 and physician global of disease damage was 34.6. Conclusions The current recruitment data confirms that pediatric patients are different from the adult patients, there is a significantly higher proportion of diffuse subset patients with 81%. 14% of the patients have overlap features. Disclosure of Interest None declared

Complement analysis reveals new biomarkers in patients with juvenile idiopathic arthritis

The juvenile idiopathic arthritis is a well researched disease in the group of autoimmunopathies. Beside the deregulation of T-cells and cytokines also the complement system is involved in the pathogenesis of this group of diseases.

Update on the juvenile systemic sclerosis inception cohort http://www.juvenile-scleroderma.com

Results We report the patient characteristics at time point 0, 6 and 12 months of their follow up. We present date on 25 patients. The mean follow up of the patients in the cohort are 3.5 years. No patient died during the follow up. Eighteen of the 25 patients were female. The mean age of the onset of Raynaud symptomatic was 10.4 years, the youngest patient was 2.0 years of age. The mean age at the onset of the non-Raynaud symptomatic were 11.0 years. 19 of the 25 have diffuse subtype, 6 of them have an overlap symptomatic, two of them associated with diffuse subtype. ANA positive were 20, and 8 of them were antiScl 70 positive. None of them was anticentromere positive The mean modified Rodnan Skin Score was at timepoint 0, 6 and 12 month 18.1, 15.1 (n=21) and 15.1. (n=17). Raynaud ́s Phenomen occurred in 22/25 at time point 0 and 16 of 21 at time point 6 months and 12 of 17 at 12 months. 18 of 25 of them had capillary changes already at time point 0. 7 of them had already ulcerations at time point zero, 9 of 21 at month 6 and 4 of 17 at months 12. 15 of them had cardiopulmonary involvement, at time point zero already, 9 of them had interstitial lung disease. 6 of 21 have cardiopulmonary involvement at month 6 and 7 of 17 at month 12 of follow up. Two of them have renal involvement at time point 0 and 3 at time point 6 and 12 months. 9 of 25 had gastrointestinal involvement, and 5 of them oesophageal involvement at time point zero, 3 from 21 at month 6 and 5 of 17 at 12 months. 22 of 25 have musculoskeletal involvement 19 of 21 at month 6 and 16 of 17 at 12 months.