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Biomedical subjects

N M Wulffraat

Publications and source records attributed to N M Wulffraat.

At least 37 records · Page 2Linked to original sources
PubMed2001

Effects of sulfasalazine treatment on serum immunoglobulin levels in children with juvenile chronic arthritis.

This article describes the effects of sulfasalazine (SSZ) treatment on serum immunoglobulin (Ig) levels in 6 children with oligoarticular- or polyarticular onset juvenile chronic arthritis (JCA). None of the children who developed dysimmunoglobulinemia during treatment showed clinical symptoms of this adverse event, in particular none developed severe infections. All patients regained normal immunoglobulin levels after discontinuing SSZ treatment. One patient with a partial IgA deficiency at the start of SSZ treatment showed a slow increase in the IgA level during treatment. During follow-up (4-6 years), one patient spontaneously developed a dysimmunoglobulinemia and one patient developed diabetes mellitus. Based on these case reports and review of the literature we advocate monitoring of serum immunoglobulin levels while on SSZ treatment.

Antirheumatic Agents↗
PubMed2000

[Immunology in the medical practice.XXXII. Transplantation of autologous hematopoietic stem cells for treatment of refractory auto-immune diseases; preliminary favorable results with 35 patients].

The objective of this study was to document the experiences in the first Dutch pilot studies of the effect of transplantation of autologous haematopoietic stem cells in patients with therapy-resistant autoimmune disease. The first results in 21 adults and 14 children are promising: remission of the disease was achieved in 13 patients, while in the others a significant reduction of disease activity was seen with a corresponding improvement of the quality of life. Infectious complications were frequently observed. Two children with systemic juvenile idiopathic arthritis developed a fatal infection-associated macrophage activation syndrome. Multicentre randomised studies are necessary to study the effects of autologous stem cell transplantation and modifications such as T-cell depletion.

Adolescent↗
PubMed2000

Identification of six novel WASP gene mutations in patients suffering from Wiskott-Aldrich syndrome.

Mutation in the gene encoding the Wiskott-Aldrich Syndrome protein (WASP) has been identified as the genetic defect responsible for WAS, an X-linked primary immunodeficiency disease characterized by eczema, thrombocytopenia, and recurrent infections. In this study, the WASP gene of 7 unrelated patients with classical WAS of Dutch descent was examined by single-strand conformation polymorphism and sequence analysis. We have identified 6 novel mutations that involve nonsense mutations (196C-->A, 344C-->T), or small deletions (553delG, 768del19, IVS8+1delGTGA, 911delT), all of which result in predicted truncation of WASP protein synthesis.

Alternative Splicing↗
PubMed2000

Myeloid-related proteins 8 and 14 are specifically secreted during interaction of phagocytes and activated endothelium and are useful markers for monitoring disease activity in pauciarticular-onset juvenile rheumatoid arthritis.

OBJECTIVE: To analyze which physiologic stimuli induce secretion of myeloid-related protein 8 (MRP8) and MRP14, two S100 proteins expressed in neutrophils and monocytes, and to determine whether serum concentrations of these proteins are reliable parameters for monitoring inflammatory activity in pauciarticular juvenile rheumatoid arthritis (JRA). METHODS: Secretion of MRP8 and MRP14 was analyzed using a coculture system of endothelial cells and monocytes. Concentrations of MRP8/MRP14 in the serum and synovial fluid of JRA patients or culture medium were determined by enzyme-linked immunosorbent assay. The expression of MRP8 and MRP14 by leukocytes in synovial tissue or fluid was investigated using immunohistochemistry. RESULTS: MRP8 and MRP14 were specifically released during interaction of activated monocytes with tumor necrosis factor-stimulated endothelial cells. Secretion was mediated via an increase in intracellular calcium levels in monocytes. In contrast, contact with resting endothelium inhibited protein kinase C-induced secretion of the proteins by monocytes. In JRA patients, MRP8 and MRP14 were strongly expressed in infiltrating neutrophils and monocytes within the inflamed joints and could be found in significantly higher concentrations in synovial fluid (mean 42,800 ng/ml) compared with serum (2,060 ng/ml). Concentrations of MRP8/MRP14 in serum correlated well with those in synovial fluid (r = 0.78) and showed a strong correlation with disease activity (r = 0.62). After intraarticular triamcinolone therapy, the serum concentrations of MRP8/MRP14 decreased significantly in therapy responders, whereas no differences were found in patients who showed no clinical benefit. CONCLUSION: MRP8 and MRP14 are specifically released during the interaction of monocytes with inflammatory activated endothelium, probably at sites of local inflammation. Their serum concentrations represent a useful marker for monitoring local inflammation in JRA.

Adolescent↗
PubMed2000

Autologous hemopoietic stem-cell transplantation for children with refractory autoimmune disease.

Autologous stem cell transplantation (ASCT) has been proposed as a possible treatment for severe autoimmune diseases such as rheumatoid arthritis (RA), multiple sclerosis (MS), systemic sclerosis, and systemic lupus erythematosus (SLE). To date, more than 250 patients with various autoimmune disorders have undergone an ASCT since 1996. Among them, there is a very limited number of children. This review summarizes the experience with ASCT for pediatric rheumatic diseases. Most reported cases concern juvenile idiopathic arthritis (JIA). Experience with ASCT for childhood SLE, Scleroderma, or Dermatomyositis is very limited. To date, 12 children with severe systemic or polyarticular JIA, all with progressive disease activity despite the use of corticosteroids, MTX, CsA, or Cyclophosphamide were treated in our center with ASCT. Rheumatologic follow-up at 3-month intervals up to 36 months showed a marked decrease in arthritis severity as expressed by the core-set criteria for juvenile chronic arthritis (JCA) activity. However, these children remain at risk for severe viral infections due to the prolonged lymfopenia. ASCT in this severely ill patient group induces a very significant and drug-free remission of the disease, but carries a significantly risk of developing fatal MAS.

Adolescent↗
PubMed1999

The depletion of T cells from haematopoietic stem cell transplants.

OBJECTIVE: In our laboratory, we have developed an immunorosette technique for the depletion of T cells from bone marrow transplants. Tetrameric complexes of monoclonal antibodies are able to form very stable immunorosettes, which are efficiently depleted with the aid of a blood cell separator. Major improvements over the original sheep red blood cell depletion are the use of human (patient or donor derived) erythrocytes instead of sheep-derived cells, and the possibility of using a closed system for separation in a cell separator. In contrast to bone marrow, mobilized haematopoietic stem cell transplants obtained after leucocytapheresis contain higher numbers of T cells. Therefore, a different approach is necessary. METHOD: We have used two CD34 selection systems (Isolex 300SA and the Clinimacs) to perform T-cell depletions from peripheral blood stem cell (PBSC) transplants. RESULTS: Immunorosette T-cell depletion, with CD2/CD3 tetrameric complexes, of bone marrow transplants resulted in a mean 2.5 log depletion of T cells with a yield of 50% of the CD34+ cell population. Stem cell selection of PBSC transplants using one of the CD34 selection procedures resulted in a 4.5 log depiction of T cells for both systems, but with different results for the recovery of CD34+ cells. An increased yield of CD34+ cells was obtained with the Clinimacs procedure (57.9+/-9.0%) in comparison to the Isolex procedure (40.1+/-12.5%). CONCLUSION: Our own immunorosette depletion technique and the two tested CD34 selection methods for stem cell transplants both resulted in a very efficient T-cell depletion with the recovery of 40-60% of the CD34 haematopoietic stem cells present in the transplant.

Antigens, CD34↗
PubMed1999

Autologous stem cell transplantation: a possible treatment for refractory juvenile chronic arthritis?

OBJECTIVE: In adults, autologous stem cell transplantation (ASCT) has been described recently as a possible treatment for severe autoimmune disease refractory to conventional treatment. We report here the four first children with severe forms of juvenile chronic arthritis (JCA) treated with ASCT. METHODS: We studied three children with systemic JCA and one child with polyarticular JCA. Unprimed bone marrow was harvested 1 month prior to ASCT. T-cell depletion of the graft was performed with CD2 and CD3 antibodies. We used a preparative regimen of antithymocyte globulin (ATG; 20 mg/kg), cyclophosphamide (Cy; 200 mg/kg) and low-dose total body irradiation (TBI; 4 Gy). Methotrexate (MTX) and cyclosporin A (CsA) were stopped before ASCT; prednisone was tapered after 2 months. RESULTS: After ASCT, our patients showed an anti-inflammatory-drug-free follow-up of 6-18 months with a marked decrease in joint swelling, pain and morning stiffness. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and haemoglobin (Hb) returned to near-normal values within 6 weeks. Despite T-cell depletion, there was a very rapid immune reconstitution. Two patients developed a limited varicella zoster virus (VZV) eruption which was treated by acyclovir.

Arthritis, Juvenile↗
PubMed1998

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group.

OBJECTIVE: To assess the efficacy, tolerability, and safety of sulfasalazine (SSZ) in the treatment of juvenile chronic arthritis (JCA). METHODS: We conducted a 24-week randomized, placebo-controlled, double-blind, multicenter study of patients with active JCA of both oligoarticular and polyarticular onset. Patients were treated with a dosage of 50 mg/kg/day of SSZ (maximum 2,000 mg/day) or placebo. The efficacy variables were joint scores, physician's, parents', and patient's overall assessments, and laboratory parameters of inflammation. RESULTS: Of the 69 patients enrolled, 52 (75%) completed the trial. Six patients (18%) withdrew from the placebo group, and 11 (31%) withdrew from the SSZ group (P = 0.18). In the intention-to-treat analysis of end point efficacy, between-group differences were significant for the overall articular severity score (P = 0.02), all global assessments (P = 0.01), and the laboratory parameters (P < 0.001). Adverse events occurred more frequently in the SSZ group and were the main reason for withdrawal (P < 0.001), but in all instances, these events were transient or reversible upon cessation of treatment. CONCLUSION: The results of this first placebo-controlled study show that SSZ is effective and safe in the treatment of children with oligoarticular- and polyarticular-onset JCA, although it was not well tolerated in one-third of the patients.

Adolescent↗
PubMed1998

Atypical juvenile generalized scleroderma presenting as polyarthritis and failure to thrive.

In this Grand Round, two children are described with atypical generalized scleroderma and severe failure to thrive. Neither had Raynaud's phenomenon nor evidence of gastrointestinal (GI) disease. Treatment with non-steroidal anti-inflammatory drugs, prednisone, D-penicillamine, alpha and gamma interferon was unsuccessful in reversing the sclerodermatous changes and growth arrest. Dietary intake analysis and extensive GI investigation were performed in both. In one case, resting energy expenditure (Ee) was repeatedly measured. His intake did not meet requirements for growth. Supplemental tube feeding (900 kcal in 6 h) was commenced, causing an increase in weight from 11 to 16 kg. The other patient refused supplementary tube feeding and no weight gain has been observed for 5 yr. In conclusion, early-onset generalized scleroderma in the absence of visceral involvement, but with growth failure, may represent an atypical form of systemic sclerosis. The response of the two patients to conventional therapy was disappointing. However, the rapid catch-up growth induced by tube feeding observed in one patient underlines the importance of adequate dietary management.

Arthritis↗
PubMed1997

Hepatic GVHD after HLA-haploidentical bone marrow transplantation in children with severe combined immunodeficiency: the effect of ursodeoxycholic acid.

We describe two children with a severe combined immune deficiency (SCID) with B cells. Following a T-cell-depleted haploidentical bone marrow transplantation (BMT), they both developed a chronic graft-versus-host disease (GVHD) of the skin and a severe persisting hyperbilirubinaemia and elevated liver enzymes. The diagnosis of a vanishing bile duct syndrome was confirmed by liver biopsies. Because corticosteroids and cyclosporin A induced only a partial response, ursodeoxycholic acid (UDCA) was added to their treatment schedule. Serum bilirubin and liver enzymes returned to normal within months. A control liver biopsy showed normal and proliferating bile ducts without cholestatic damage. We conclude that UDCA was well tolerated and may be of value as an additional treatment for hepatic GVHD in SCID.

Adrenal Cortex Hormones↗