Clinical aspects of paediatric mastocytosis: a review of 101 cases.

BACKGROUND: Cutaneous mastocytosis (CM) is a typical presentation of mastocytosis in children. However, systemic mastocytosis may also occur in children. OBJECTIVE: We tried to characterize the clinical features of childhood-onset mastocytosis and estimate the value of the SCORMA (SCORing Mastocytosis) Index and serum tryptase levels as disease severity parameters. METHODS: In a survey of 101 children mastocytosis was diagnosed and classified according to World Health Organization criteria. In all the cases serum tryptase levels and the SCORMA Index were done to assess the extent and intensity of the disease. RESULTS: Cutaneous mastocytosis was diagnosed in 100 children; 84% of them presented maculopapular CM, 10% mastocytoma and 6% diffuse cutaneous mastocytosis. Moreover, systemic mastocytosis with bone marrow infiltration and associated with maculopapular CM was found in one case. There was a positive correlation of serum tryptase level to the SCORMA Index. Both the mean tryptase level and the mean SCORMA Index were elevated in diffuse cutaneous mastocytosis children when compared with other forms CM. A significantly higher mean tryptase level was found in children with flushing, hypotension, diarrhoea, extensive bullous lesions and osteoporosis or osteopenia. CONCLUSION: Mastocytosis in children usually has a benign course. Nevertheless, severe mediator-related symptoms and systemic involvement may appear. Therefore, a multidisciplinary approach involving careful monitoring of the serum tryptase level, SCORMA Index and the organ function is recommended. Both tryptase levels and the SCORMA Index are of a great value as disease severity parameters and they should be assessed simultaneously in all mastocytosis patients.

Interleukin-13 promoter gene polymorphism -1112C/T is associated with the systemic form of mastocytosis.

BACKGROUND: Mastocytosis is a heterogenous disease involving mast cells (MC) and their progenitors. Cutaneous and systemic variants of the disease have been reported. In contrast to cutaneous mastocytosis (CM), patients with systemic mastocytosis (SM) are at risk to develop disease progression or a nonMC-lineage haematopoietic neoplasm. Little is known, however, about factors predisposing for the development of SM. One factor may be cytokine regulation of MC progenitors. METHODS: We examined the role of the interleukin-13 (IL-13) promoter gene polymorphism -1112C/T, known to be associated with increased transcription, in mastocytosis using allele-specific polymerase chain reaction method. Serum tryptase and IL-13 levels were determined by immunoassay, and expression of the IL-13 receptor in neoplastic MC by reverse transcription-polymerase chain reaction and flow cytometry. RESULTS: The frequency of the -1112T allele of the IL-13 promoter was significantly higher in patients with SM compared with CM (P < 0.008) and in mastocytosis patients compared with healthy controls (P < 0.0001). Correspondingly, the polymorphism was found to correlate with an elevated serum tryptase level (P = 0.004) and with adult-onset of the disease (P < 0.0015), both of which are almost invariably associated with SM. Serum IL-13 levels were also higher in SM patients compared with CM (P = 0.011), and higher in CT- than in CC carriers (P < 0.05). Finally, we were able to show that neoplastic human MC display IL-13 receptors and grow better in IL-13-containing medium. CONCLUSIONS: The -1112C/T IL-13 gene polymorphism and the resulting 'hypertranscription' may predispose for the development of SM.

Persistence of protein oxidation products and plasma antioxidants in juvenile idiopathic arthritis. A one-year follow-up study.

OBJECTIVE: Plasma protein oxidation products and blood antioxidants, like superoxide dismutase (SOD), glutathione peroxidase (GPx) and total antioxidant status (TAS) were investigated in children with juvenile idiopathic arthritis (JIA) in a year follow-up study. METHODS: Carbonyl group content within plasma proteins, activity of red blood cell SOD and GPx, as well as the blood TAS level were determined in 14 children with JIA twice, namely at the admission to the hospital (Time 0 = T0) and then after a year of treatment (Time 1 = T1). RESULTS: An increased level of plasma protein carbonyls was observed in both assessments (T0 and T1) as compared to control. However there was no significant difference in plasma carbonyls level between the initial (T0) and final (T1) examination of the patients. Similarly, SOD activity was higher in children with JIA as compared to control subjects and did not change significantly after a year of follow-up. Red blood cell GPx activity remained within the normal range throughout the study. Interestingly, the blood TAS level was initially comparable to control and rose significantly after the year of treatment. CONCLUSION: A level of plasma protein oxidation products remains significantly higher in children with JIA as compared to healthy subjects. The lack of accumulation of plasma protein carbonyls may result from efficient proteolysis in childhood and/or adaptive increase of the blood TAS level in the course of effective anti-inflammatory therapy. Analysis of plasma oxidative stress markers and antioxidant potential of the blood might be helpful in monitoring the clinical treatment of children suffering from JIA.

Preferential immunoglobulin oxidation in children with juvenile idiopathic arthritis.

OBJECTIVE: Juvenile idiopathic arthritis (JIA) is a rare chronic inflammatory disorder of the joints. There is strong evidence that oxidative damage occurs in rheumatoid diseases, including JIA. The increased level of protein oxidation products in total plasma proteins has recently been reported in children with diagnosed JIA. The objective of this study was to find out which fraction of plasma proteins is mostly damaged by oxidative stress and whether the damaging effect correlates with certain clinical or laboratory parameters. METHODS: A new approach to estimate the carbonyl content of plasma protein fractions was developed, based on two-stage electrophoresis and immunochemical detection of the carbonyl derivatives of the proteins. This method allowed us to detect and quantitate carbonyl groups in the albumin, alpha-2, beta and gamma-globulin fractions. Sera of 25 children with JIA and 13 healthy controls were tested. RESULTS: Albumin and gamma-globulins were found to be most modified by oxidation. In a group of children with systemic JIA, both albumin and gamma-globulins were oxidized while plasma gamma-globulin fraction damage was prevalent in pauciarticular JIA. CONCLUSIONS: Among plasma proteins of children with JIA, gamma-globulins were preferentially oxidized, whereas most of the other proteins did not seem to be affected. Oxidative modification of plasma proteins was correlated with the type of JIA. These findings may allow the use of carbonyls as clinical markers of inflammatory process activity in patients with different types of JIA. It is also a potential tool for monitoring oxidative protein damage in other diseases and therapies.

Protein carbonyl groups' content as a useful clinical marker of antioxidant barrier impairment in plasma of children with juvenile chronic arthritis.

The purpose of our study was to find out the intensity of free radical reactions in pediatric patients with different forms of juvenile chronic arthritis (JCA) on the basis of carbonyl groups' content in plasma proteins, evaluated with the use of Levine's method. We examined a population of 52 children with diagnosed JCA of different types and activities in the study. The carbonyl groups' content in plasma proteins of ill children was significantly higher than in healthy group (1.36 +/- 0.68 vs. 0.807 +/- 0.16 nmol/mg of protein). The carbonyls increased parallell with the activity of the disease; their content was significantly higher in children with high-disease activity than in children with medium- or low-disease activity. Moreover, children with oligoarthritis had carbonyls level 1.09 +/- 0.59 nmol/mg of protein, vs. 1.62 +/- 0.82 in children with systemic type of JCA. The values of carbonyls in children with polyarthritis were and 1.36 +/- 0.50 nmol/mg of protein. Correlation between the carbonyl groups content and the activity or the type of JCA may allow use of carbonyls as a clinical marker of antioxidant barrier impairment in this group of patients. This aspect of the disease may undergo pharmacologic modification in future.

[Carbonyl groups content on the basis of protein peroxidation analysis with total antioxidant status in blood of children with cancers]. / Ocena aktywnosci reakcji wolnorodnikowych na podstawie analizy peroksydacji bialek w powiazaniu z calkowita obrona przeciwutleniaczowa krwi u dzieci z choroba nowotworowa.

Toxic oxygen free radicals have been implicated as important pathologic mediators in carcinogenesis. Several reports have found antioxidants and enzymes related to the antioxidants function at increased or decreased levels in blood of patients with cancers. In previous publications we observed that antioxidant barrier can be different in healthy children and children with cancers. This time we were looking for a stable marker of damaging effect of free radicals reactions in association with antioxidant barrier in blood. Carbonyl group level in proteins has been introduced as a good marker of oxidative stress damage. For this study we selected 60 children at the age of 3 to 16, who had been diagnosed as suffering from cancers: malignant (m) bone tumors (t) (n = 25), m. brain t. (n = 20), lymphoma malignum (n = 5), m. liver t. (n = 5) and m. germ cell t. (n = 5). The control group consisted of 40 age-matched healthy children (22 boys and 18 girls). We investigated the concentration of carbonyl groups (CG) in serum spectrofotometrically, according to the method of Levine. Plasma total antioxidant status (TAS) was estimated colorometrically with radical cation ABTS (2,2'-Azino di-[3-ethylbenzthiazoline sulphonatel]), erythrocyte glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were assessed according to the method of Paglia & Valentine and Minami & Yoshikawa respectively (Kits of Randox Laboratories Ltd.). In this study the content of CG in plasma proteins has shown a significant increase (1.60 +/- 0.77 vs 0.78 +/- 0.15 nmol/mg protein, p < 0.001) and erythrocyte GSH-Px activity has shown a significant decrease (16.3 +/- 7.9 vs 25.1 +/- 15.8 U/gHb, p < 0.02) in children with malignant tumors. No differences were observed in SOD activity and TAS between sick and healthy children. A possible interpretation of this data suggests an inadequate antioxidants' protection in children with cancers. The relationship between the oxidative damage and carcinogenesis requires further investigations.