Young patients with both type 1 diabetes mellitus and asthma have a unique IL-12 and IL-18 secretory pattern

Rachmiel M, Bloch O, Shaul AA, Ben‐Yehudah G, Bistritzer Z, Weintrob N, Ofan R, Rapoport MJ. Young patients with both type 1 diabetes mellitus and asthma have a unique IL‐12 and IL‐18 secretory pattern. Background: The expression of the regulatory cytokines interleukin (IL)‐12 and IL‐18 in patients with both Th1‐ and Th2‐mediated diseases, type 1 diabetes mellitus (T1DM) and asthma, is unknown. Objective: To investigate the in vivo and in vitro IL‐12 and IL‐18 secretion patterns in patients with both T1DM and asthma. Methods: Peripheral blood mononuclear cells (PBMC) were collected from 44 patients. Mean age 19.4 ± 4.7 yr (10.5–28 yr), divided into four paired groups: T1DM and asthma, asthma only, T1DM only, and healthy controls. T‐cell proliferative response was assessed. IL‐12 and IL‐18 serum levels and expression by PBMC following in vitro stimulation by lipopolysaccharide (LPS) were determined by enzyme‐linked immunosorbent assay (ELISA). Results: Patients with T1DM and asthma had higher serum levels of both IL‐12 and IL‐18 compared to controls: 146.2 ± 69.2 and 109.7 ± 34.6 pg/mL, p = 0.038 and 436.1 ± 117.9, 320.2 ± 99.1 pg/mL, p = 0.028, respectively. Stimulated IL‐12 secretion was significantly lower in these patients compared to those with one disease only: 809 ± 426.4, 2111.6 ± 2214.3, 3188.1 ± 2692.9 pg/mL and after 48 h: 956.3 ± 489.3, 2429.8 ± 2394.6, 3874.5 ± 2820.3 pg/mL, respectively, p < 0.03 for all. The IL‐18/IL‐12 serum ratio was also significantly higher in patients with both diseases compared to those with asthma only, p = 0.017. Conclusion: Patients with both T1DM and asthma display a different pattern of IL‐12 and IL‐18 expression compared to patients with one disease only and controls.     

Increased serum‐soluble interleukin‐5 receptor alpha level precedes the development of eczema in children

Semic‐Jusufagic A, Gevaert P, Bachert C, Murray C, Simpson A, Custovic A. Increased serum‐soluble interleukin‐5 receptor alpha level precedes the development of eczema in children.
Pediatr Allergy Immunol 2010: 21: 1052–1058.
© 2010 John Wiley & Sons A/S Interleukin‐5 receptor α‐subunit expression may be implicated in the development of allergic diseases. In a population‐based birth cohort, we investigated the relationship between IL‐5Rα and the development of allergic phenotypes in childhood, using soluble IL‐5Rα (s‐IL‐5Rα) as a marker. Children (n = 510) were followed from birth and assessed at age 3, 5 and 8. Based on the onset and resolution of symptoms, we assigned children into the following wheeze and eczema phenotypes: never, transient, persistent, intermittent and late‐onset. Specific IgE to common allergens, s‐IL‐5Rα (ELISA) and urinary eosinophilic protein X (U‐EPX) levels was measured at age 5. s‐IL‐5Rα was significantly higher among atopic compared to non‐atopic children (pg/ml, geometric means [95% CI], 152.4 [126.0–184.5] vs. 103.4 [94.0–113.9], p < 0.0001). While we found no association between s‐IL‐5Rα and current eczema at age 5, there was a significant association between eczema phenotypes and s‐IL‐5Rα (multiple anova model adjusted for gender and atopy, F = 2.56, p = 0.04). After adjustment for multiple comparisons, we found that children with late‐onset eczema had significantly higher s‐IL‐5Rα compared to those who have never had eczema (mean difference [95% CI], 2.41 [1.03–5.62], p = 0.04) and those with intermittent eczema (2.63 [1.08–6.41], p = 0.02), with no difference between children who have never had eczema and other eczema phenotypes. We found no such association for wheeze phenotypes. There was a weak correlation between s‐IL‐5Rα and U‐EPX (r = 0.16, p < 0.0001). Increased serum s‐IL‐5Rα level at age 5 was associated with contemporaneous atopic sensitization and with subsequent development of eczema by age 8.     

IL‐17E but not IL‐17A is associated with allergic sensitization: results from the LISA study

Herberth G, Daegelmann C, Röder S, Behrendt H, Krämer U, Borte M, Heinrich J, Herbarth O, Lehmann I for the LISAplus study group. IL‐17E but not IL‐17A is associated with allergic sensitization: results from the LISA study.
Pediatr Allergy Immunol 2010: 21: 1086–1090.
© 2010 John Wiley & Sons A/S Functional studies have provided evidence for the importance of IL‐17A and IL‐17E in the regulation of immune responses. IL‐17A is involved in inflammation and IL‐17E is able to induce Th2 cytokine production and eosinophilia. By now it is not clear whether these cytokines correlate with specific IgE levels. The aim of our investigation was to analyse the relationship of these two cytokines to allergic sensitization in context of an epidemiological study. Within the Life style Immune System Allergy study (LISA), we analysed phytohemagglutinin (PHA)‐stimulated blood samples of 6 yr old children for the concentration of IL‐17A and IL‐17E and sera for levels of specific IgE. In total, data from 293 children were available for blood analysis and for the analysis of confounding factors for the allergic sensitization. Among the investigated children, 29% reacted against inhalant and 13.6% against food allergens, whereas 33.1% of children were sensitized to any allergen. IL‐17E was associated with high levels of any specific IgE (adjusted odds ratio (OR) 1.45, 95% confidence interval (CI) 1.11–1.90). Furthermore, children with high IL‐17E responses (>208.8 pg/ml) were sensitized to food and inhalant allergens (OR 1.45, 95% CI 1.02–2.07 and OR 1.35, 95% CI 1.03–1.77, respectively) and to Der p 1 (OR 1.55, 95% CI 1.12–2.15). In contrast, IL‐17A, in trend, was negatively associated to sensitization to timothy (p for trend=0.013) and rye (p for trend=0.026). Concluding IL‐17E production is linked to the amount of specific IgE antibodies in blood samples of 6 yr old children.     

Neonatal BCG vaccination induces IL‐10 production by CD4+ CD25+ T cells

Akkoc T, Aydogan M, Yildiz A, Karakoc‐Aydiner E, Eifan A, Keles S, Akin M, Kavuncuoglu S, Bahceciler NN, Barlan IB. Neonatal BCG vaccination induces IL‐10 production by CD4⁺ CD25⁺ T cells.
Pediatr Allergy Immunol 2010: 21: 1059–1063.
© 2010 John Wiley & Sons A/S To determine the optimal time of Bacillus Calmette–Guerin (BCG) vaccination for induction of Th1 immunity, we measured the interferon (IFN)‐γ and interleukin (IL)‐10 secretion in purified protein derivative (PPD)‐stimulated peripheral blood mononuclear cell (PBMC) cultures in newborns vaccinated at birth or 2nd month of life. Moreover, role of CD4⁺ CD25⁺ T cells was studied by depletion assay at 8th month. Nineteen term and healthy newborns were randomized into two groups: Group I composed of 10 newborns vaccinated with BCG at birth and the remaining 9 (group II) at 2nd month of life. PBMCs were isolated at birth, 2nd and 8th months of age, and PPD‐stimulated IL‐10, 5 and IFN‐γ secretion were assessed. The same measurements were repeated for IL‐10 and IFN‐γ after the depletion of CD4⁺ CD25⁺ T cells at the 8th month. Children vaccinated at birth demonstrated higher PPD‐stimulated IFN‐γ and IL‐10 levels at 2 months of age when compared to non‐vaccinated ones (p = 0.038 and p = 0.022, respectively), whereas at 8 months, no significant differences were detected between the two groups. Moreover, CD4⁺ CD25⁺‐depleted T‐cell cultures resulted in lower PPD‐stimulated IL‐10 levels in those vaccinated at birth when compared to non‐depleted condition at the 8th month (p < 0.001). BCG at birth upregulated PPD‐stimulated IFN‐γ secretion at the 2nd month and remained still detectable at 8 month after the vaccination, whereas those vaccinated at the 2nd month of life lacked that increase in IFN‐γ response at the same time‐point. Furthermore, depletion assays suggest that CD4⁺ CD25⁺ T cells are involved in PPD‐stimulated IL‐10 secretion in response to BCG vaccination.     

Unrelated donor hematopoietic stem cell transplantation for infantile enteropathy due to IL‐10/IL‐10 receptor defect

Recent advances in genetic diagnosis have identified mutations in gene encoding interleukin‐10 (IL‐10) and IL‐10 receptor (IL‐10R) proteins as a cause for early‐onset enterocolitis leading to hyperinflammatory immune response. Allogeneic HSCT offers a potential cure; however, it was only performed in a few infants and mainly from family‐related donors. We report a case of a girl who presented very early in life with severe infantile enterocolitis. Gene sequencing confirmed IL‐10R defect. Her older sister died at 13 months of age from severe undiagnosed enterocolitis. There was no family donor. An unrelated search identified a potential 10/10 high‐resolution HLA‐matched donor. There was some delay in donor activation because IL‐10R defect was not on the standard list of indications for unrelated HSCT. Our patient received the unrelated HSCT at seven months of age, and she is currently nine months after transplant and doing very well. Because HSCT is the curative option of choice for this disorder, we encourage adding IL‐10 and IL‐10R protein defects to the list of HSCT indications for unrelated donor procurement.     

Cytokines in human milk and late‐onset breast milk jaundice

Background: Maternal milk plays an important role in the development of late‐onset breast milk jaundice (BMJ), possibly due to the unique characteristics of breast milk. The aim of this study was to investigate whether there is a relation between cytokine concentrations in the milk of nursing mothers and BMJ. Methods: Breast milk samples were collected from breast‐feeding mothers of healthy full‐term neonates, 40 with BMJ and 40 without jaundice. Milk samples were taken between the second and the fourth postpartum week. The concentrations of interleukin (IL)‐1 β, IL‐6, IL‐8, IL‐10, and tumor necrosis factor‐α were measured by flow cytometric bead array. Results: There were significant differences between the study groups in terms of IL‐1 β concentrations (P= 0.013). Not statistically significant but similar trends were also seen for IL‐10 (P= 0.067) and tumor necrosis factor‐α (P= 0.053) concentrations. However, no significant differences were noted in IL‐6 (P= 0.174) and IL‐8 (P= 0.285) concentrations. Conclusions: IL‐1 β concentration seems to be increased in milk of mothers whose infants had BMJ. Although the effect of these cytokines on BMJ is unknown, it may cause prolonged jaundice via hepatic uptake, hepatic excretion, conjugation and intestinal absorption.     

Exploring beyond viral load testing for EBV lymphoproliferation: Role of serum IL‐6 and IgE assays as adjunctive tests

Barton M, Wasfy S, Hébert D, Dipchand A, Fecteau A, Grant D, Ng V, Solomon M, Chan M, Read S, Stephens D, Tellier R, Allen UD and the EBV and Associated Viruses Collaborative Research Group. Exploring beyond viral load testing for EBV lymphoproliferation: Role of serum IL‐6 and IgE assays as adjunctive tests.
Pediatr Transplantation 2010: 14: 852–858. © 2010 John Wiley & Sons A/S. Abstract: We examined serum IL‐6 and IgE assays as adjuncts to VL monitoring for PTLD. Paediatric solid organ transplant recipients were followed with VL monitoring. VL, IL‐6, and IgE assays were compared between PTLD cases and non‐cases at <3, 3–6 and >6 months after transplantation. Median IL‐6 levels in PTLD cases were 15.5 (2.0–87.1) and 23.3 (2.1–276) pg/mL compared with 3.25 (0.92–114) and 3.5 (0.75–199.25) pg/mL in non‐cases at 3–6 and >6 months, respectively (p = 0.006 and p = 0.005). At >6 months, IL‐6 levels correlated with VL and PTLD occurrence (Spearman’s coefficients = 0.40; p = 0.001 and 0.32; p = 0.003) in univariate analyses. No benefit was derived from performance of IgE levels. The sensitivity and specificity of high VL as a test of PTLD were 76.3% and 92.5%, while the negative predictive value and PPV of VL were 94.9% and 68.4%, respectively. Combining elevated IL‐6 with high VL increased the PPV and specificity to 80% and 96.2%, respectively, and improved the receiver operating characteristic curve. Serum IL‐6 levels can improve the clinician’s ability to identify PTLD, among patients with elevated EBV viral loads.     

Elastase, α1‐proteinase inhibitor,and interleukin‐8 in pre‐dialyzed and hemodialyzed patients with chronic kidney disease

Background: Neutrophil elastase in complex with α₁‐proteinase inhibitor (NE‐α₁PI) and interleukin (IL)‐8 may serve as indicators of neutrophil activation and inflammatory stage. The aim of the study was to evaluate NE‐α₁PI, α₁‐PI, and IL‐8 levels in the blood of patients with chronic kidney disease (CKD) undergoing hemodialysis (HD) or conservatively treated (CT). The influence of a single HD session on the investigated parameters was also assessed. Methods: Blood samples were obtained from two groups of hemodialyzed patients (children/young adults [group HD1, n= 8] and adults [group HD2, n= 13]), as well as 13 CT patients and a group of healthy subjects. The proteins were measured using enzyme‐linked immunosorbent assay or radial immunodiffusion. Results: There were no significant differences in NE‐α₁PI, α₁‐PI, and IL‐8 concentrations between the HD1 and HD2 patients. The levels of NE‐α₁PI were considerably higher than normal in both groups of HD patients (before and after the HD session) and in the CT patients. Higher titers of NE‐α₁PI (P < 0.05) and α₁‐PI (P < 0.01) were obtained in the adults during the course of HD. Increased NE‐α₁PI was positively correlated with α₁‐PI. The serum concentration of IL‐8 was significantly higher in the HD2 patients before and after dialysis than in the controls. Conclusions: The data indicate that in CKD patients, neutrophils are highly activated both in the pre‐dialyzed period and on regular HD. Contact with the dialysis membrane during HD causes a significant increase in blood NE‐α₁PI and α₁‐PI in adults, but not in children/young adults. NE‐α₁PI seems to be a much better indicator of an inflammatory state in CKD patients than free α₁‐PI or IL‐8.     

Therapeutic response of metastatic angiomatoid fibrous histiocytoma carrying EWSR1‐CREB1 fusion to the interleukin‐6 receptor antibody tocilizumab

Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue tumor that has been associated with EWSR1‐CREB1 gene fusion. Outcome in patients with unresectable distant metastases is generally fatal. Interleukin‐6 (IL‐6) secretion has been described in tumors with EWSR1‐CREB1 fusion, and may promote tumor growth due to autocrine stimulation. Tocilizumab is an IL‐6 receptor antibody that has potential benefit as a targeted therapy in refractory neoplasms with IL‐6 secretion. We describe a child with metastatic AFH with EWSR1‐CREB1 fusion and elevated IL‐6 whose disease progressed during treatment with traditional chemotherapeutic agents, but improved after targeted therapy with tocilizumab.     

High production of interleukin‐10 and interferon‐γ in influenza‐associated MERS in the early phase

Mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) occurs in various diseases and pathologies, and the clinical symptoms are not consistent with the impaired region. The mechanism of the region specificity is unclear. We investigated the cytokine profiling in cerebrospinal fluid (CSF) and serum obtained from a child with MERS during influenza infection, and compared them with those of serious another serious type of influenza‐associated encephalopathy. There was no elevation of Interleukin (IL)‐1β, which induces convulsion. The inhibitory cytokines of IL‐10 and IFN‐γ were elevated in the early phase in CSF. Comparing them with other patients, the elevation of the cytokine levels were generally mild. Considering that the prognosis of this MERS case was favorable and high levels of inhibitory cytokines including IL‐10 and IFN‐γ might work to localize the lesion and to prevent sequelae.     

Relation between serum IL‐4, IL‐13 and IFN‐γ levels and recurrence of wheezing episodes in infants with acute bronchiolitis

Lower respiratory tract infections are the most important factors among various causes which trigger wheezing in the first year of life. The factors associated with episodic wheezing in children with acute bronchiolitis are still subjects of research. Infections, environmental factors, immunologic mechanisms are sorted as etiologic risk factors of episodic wheezing. We aimed to investigate the relationship between serum interleukin (IL)‐4, IL‐13 and γ‐interferon (IFN‐γ) levels and recurrence of wheezing episodes in infants with acute bronchiolitis. One hundred twenty infants between 3 and 36 months with acute bronchiolitis enrolled in the study. Personal histories, clinical and laboratory data of infants were recorded. The patients were followed for a year. Venous blood samples were obtained to determine serum IL‐4, IL‐13, and IFN‐γ levels during acute bronchiolitis episode. The number of wheezing episodes was significantly higher in infants with a positive family history of allergy. A statistically significant correlation was determined between serum IL‐13 levels of infants and number of wheezing episodes. High serum IL‐13 levels and a positive history of allergy may have important roles in the recurrence of acute bronchiolitis.     

The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis

Choi J, Callaway Z, Kim HB, Fujisawa T, Kim CK. The role of TNF‐α in eosinophilic inflammation associated with RSV bronchiolitis.
Pediatr Allergy Immunol 2010: 21: 474–479.
© 2009 John Wiley & Sons A/S The purpose of our study was to investigate whether tumor necrosis factor (TNF)‐α correlates with eosinophilic inflammation that occurs during a lower respiratory tract infection with the respiratory syncytial virus (RSV) in children. Sixty children with RSV bronchiolitis (RSV group) and 20 healthy children with no respiratory symptoms (Control group) were enrolled. We measured the nasal lavage fluid (NLF) Th2 cytokine (IL‐5), proinflammatory cytokine (TNF‐α, IL‐8), eosinophil‐active cytokine [granulocyte‐macrophage colony stimulating factor (GM‐CSF), IFN‐γ], and eosinophil‐active chemokine (eotaxin, regulated on activation normal T cell excreted and secreted) levels for both groups. We also measured serum eosinophil‐degranulation product (eosinophil‐derived neurotoxin; EDN, eosinophil cationic protein; ECP) levels from RSV group. TNF‐α, IL‐8, GM‐CSF, IFN‐γ, and eotaxin levels were significantly higher in the RSV group compared with the Control group. TNF‐α correlated with GM‐CSF (r = 0.87, p < 0.0001), IFN‐γ (r = 0.92, p < 0.0001), eotaxin (r = 0.64, p < 0.0001), and IL‐8 (r = 0.84, p < 0.0001). TNF‐α may have an important role in eosinophilic inflammation of airways in children with RSV bronchiolitis.     

Determination of T‐cell subpopulations and intracellular cytokine production (interleukin‐2, interleukin‐4, and interferon‐γ) by cord blood T‐lymphocytes of neonates from atopic and non‐atopic parents

This report describes the results of a prospective study on immunological markers in cord blood for the prediction of allergic diseases in children. First we evaluated methodological aspects of the flow cytometric technique on cord blood cytokine measurements. Subsequently, the T‐cell subsets and percentage of cytokine‐producing cord blood T‐helper (Th) and T‐suppressor/cytotoxic lymphocytes of neonates from atopic and non‐atopic parents were compared. A group of 33 healthy, full‐term newborn infants of whom 23/33 were at risk for atopy (i.e. having at least one parent with one or more atopic symptoms and positive specific immunoglobulin E [IgE] to at least one common inhalant allergen) was studied. A flow cytometric technique was used to analyze cord blood T‐cell subsets and to determine the percentage of interleukin (IL)‐2‐, IL‐4‐, and interferon‐γ (IFN‐γ)‐producing cord blood Th and T‐suppressor/cytotoxic lymphocytes following stimulation with phorbol 12‐myristate 13‐acetate (PMA) and ionomycin. The percentage of CD3 (T lymphocytes), CD3⁺ CD4⁺ (Th lymphocytes), CD3⁺ CD8⁺ (T‐suppressor/cytotoxic lymphocytes), CD19⁺ (B lymphocytes), CD3⁺ CD4⁺ CD45RO⁺ (memory Th lymphocytes), and CD3⁺ CD4⁺ CD45RA⁺ (naive Th lymphocytes) cells was unrelated to parental atopic status. PMA stimulation augmented the percentage of IL‐2‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes, whereas the number of IL‐4‐producing T lymphocytes remained very low or undetectable. No differences in the percentage of IL‐2‐, IL‐4‐ and IFN‐γ‐producing Th and T‐suppressor/cytotoxic lymphocytes were found between neonates from atopic and non‐atopic parents. These results will be re‐evaluated when the atopic status of the children at the age of 1 and 2 years can be assessed.     

Relationships among specific viral pathogens,virus‐induced interleukin‐8, and respiratory symptoms in infancy

Both virus‐mediated damage to airway tissues and induction of pro‐inflammatory cytokines such as interleukin‐8 (IL‐8) could contribute to symptom severity during viral respiratory infections in children. To test the hypothesis that IL‐8 contributes to the pathogenesis of respiratory symptoms during naturally acquired respiratory viral infections in children, nasal wash samples collected from infants with acute viral infections (n = 198) or from healthy uninfected infants (n = 31) were analysed for IL‐8. Nasal wash IL‐8 was positively related to age in uninfected children (r_s = 0.36, p < 0.05). Respiratory syncytial virus (RSV) infection caused more severe respiratory symptoms compared to infections with influenza A, parainfluenza viruses, or rhinoviruses. In addition, RSV, parainfluenza and rhinovirus infections increased levels of IL‐8 in nasal lavage fluid, and there were some differences in the ability of the viruses to induce IL‐8 production (RSV>influenza, p < 0.05). Finally, there were significant correlations between nasal wash IL‐8 levels and symptom scores during infections with rhinovirus (r_s = 0.56, p < 0.001) or influenza A (r_s = 0.45, p < 0.05), but not with parainfluenza virus or RSV. These findings provide evidence of a close relationship between the generation of IL‐8 and symptoms during acute community‐acquired infections with rhinovirus or influenza A. In contrast, for RSV and parainfluenza infections, factors in addition to IL‐8 production appear to contribute to the generation of clinical symptoms.     

The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma*

Korematsu S, Yamamoto K, Nagakura T, Miyahara H, Okazaki N, Akiyoshi K, Maeda T, Suenobu S‐i, Izumi T. The indication and effectiveness of low‐dose erythromycin therapy in pediatric patients with bronchial asthma.
Pediatr Allergy Immunol 2010: 21: 489–492.
© 2010 John Wiley & Sons A/S To elucidate the mechanisms of intractable pediatric bronchial asthma and the indication of low‐dose erythromycin (EM) therapy, the serum chemokine levels of and the angiogenic factor were evaluated in 55 pediatric patients with bronchial asthma; 7.4 ± 3.5 yr old, who had been treated with inhaled steroid, leukotriene receptor antagonist, theophylline and others for more than a year. Both the levels of interleukin (IL) 8 (p = 0.036) and vascular endothelial growth factor (VEGF) (p = 0.005) were higher in patients with severe type than those of patients with the milder type, while other chemokine levels such as serum eotaxin and MCP1 did not show the correlation with the severity of bronchial asthma. Induction of therapy with low‐dose EM induced improvement of the clinical symptoms in patients with severe type and decrease of their serum chemokine levels: IL8; from 736 ± 88 to 75 ± 85 pg/ml (p < 0.0005), and VEGF; from 352.0 ± 160.5 to 132.2 ± 59.9 pg/ml (p = 0.021) within the next 6 months. Moreover, low‐dose EM resulted in a decreased daily peak‐trough fluctuation rate of the serum theophylline concentration; (C_max ? C_min)/C_min, from 1.3 ± 0.5 to 0.5 ± 0.3, which led to the maintenance of effective serum levels. These results indicated that IL8 and VEGF affect the severity of standard therapies resistance intractable bronchial asthma. Through the suppression of these chemokines and maintenance of effective theophylline levels, low‐dose EM therapy improves the symptoms of bronchial asthma.     

Induction regimens and post‐transplantation lymphoproliferative disorder after pediatric intestinal transplantation: Single‐center experience

Pediatric recipients of intestinal transplants have a high incidence of PTLD, but the impact of specific induction immunosuppression agents is unclear. In this single‐center retrospective review from 2000 to 2017, we describe the incidence, characteristics, and outcomes of PTLD after primary intestinal transplantation in 173 children with or without liver, after induction with rATG, alemtuzumab, or anti‐IL‐2R agents. Thirty cases of PTLD occurred among 28 children, 28 EBV+ and 2 EBV?. Although not statistically significant, the PTLD incidence was higher after isolated intestinal transplant compared with liver‐inclusive allograft (19.3% vs 13.3%, P = .393) and after induction with anti‐IL‐2R antibody and alemtuzumab compared with rATG (28.6% and 27.3% vs 13.3%, P = .076). The 30 PTLD cases included 13 monomorphic PTLD, 13 polymorphic PTLD, one spindle cell, one Burkitt lymphoma, and two cases too necrotic to classify. After reduction of immunosuppression, management was based on disease histology and extent. Resection with or without rituximab was used for polymorphic tumors and limited disease extent, whereas chemotherapy was used for diffuse disease. Of the 28 patients, 11 recovered with functioning allografts (39.3%), 10 recovered after enterectomy (35.7%), and seven patients died (25%), three due to PTLD and four due to other causes. All who died of progressive PTLD had received chemotherapy, highlighting the mortality of PTLD, toxicity of treatment and need for novel agents. Alemtuzumab is no longer used for induction at our center.     

Possible pathologenic role of interleukin-5 and eosino cationic protein in Henoch-Schönlein purpura nephritis

Abstract Background : The mechanism for the onset of Henoch‐Schönlein purpura nephritis is unknown. In order to identify the pathogenesis of nephritis, laboratory findings and serum cytokines between Henoch‐Schönlein purpura (HSP) patients without nephritis and with nephritis were investigated. Methods : We enrolled 32 patients who had been diagnosed with HSP from January 1993 to December 1998. These patients were divided into two groups. Group 1 consisted 12 patients without nephritis and group 2 consisted 20 patients with nephritis. We evaluated laboratory findings such as eosinophil counts, serum IgE, eosino cationic protein (ECP), and serum cytokine (interleukin (IL)‐2, IL‐4, IL‐5, IL‐6, IL‐10, IL‐13 interferon‐γ and tumor necrotic factor‐α) concentrations between both groups. Results : At the acute phase, serum IL‐5 and ECP concentrations in group 2 were higher than those in group 1 (59.4 ± 32.7 pg/mL vs. 10.8 ± 12.8 pg/mL, P < 0.05, 24.3 ± 5.1 µg/L vs. 8.9 ± 4.2 µg/L, P < 0.05, respectively). Serum IL‐4 concentrations at the acute phase in group 1 were higher than those in group 2 (40.2 ± 21.5 pg/mL vs. 10.7 ± 5.4 pg/mL, P < 0.01). In group 2, serum IL‐5 concentrations at the acute phase were higher than those at recovery phase. Conclusions : These findings suggest that IL‐5 and eosinophil activation may be one of the factors involved in the mechanism for onset of nephritis.