High soluble interleukin-2 receptor values in Indian paediatric & adult controls - Need for population-specific threshold in the diagnosis of haemophagocytic lymphohistiocytosis.

Background & objectives: Elevated soluble interleukin-2 receptor (sIL2R) is a diagnostic criterion for haemophagocytic lymphohistiocytosis (HLH). International guidelines propose a 2400 U/ml cut-off or individual laboratory-defined cut-off. However, sIL2R normal values are so far not known in Indians. So, this study was undertaken to measure sIL2R in healthy children and adults to establish age-related reference values. Methods: Healthy controls and cases (participants with persistent fever, organomegaly, cytopenias and biochemical markers of HLH) were prospectively enrolled. Serum sIL2R was measured by double-sandwich enzyme immunoassay in a standardization batch to determine the optimum cut-off value using receiver operator characteristic curve and was subsequently validated. Results: One hundred and forty six age- and sex-matched children (80 controls and 66 suspected HLH cases) and 55 adults (49 controls and 6 suspected HLH cases) were prospectively enrolled. The optimal sIL2R cut-off ≥23 ng/ml was defined as raised sIL2R in the standardization batch. No controls had sIL2R ≥23 ng/ml in the validation batch. In healthy controls, median sIL2R (interquartile range) decreased with increasing age from 9.0 ng/ml (6.6-13.4) below five years of age to 3.2 ng/ml (2.8-5.1) in adults. Proposed upper limit of normal value for sIL2R is 17.4 ng/ml in less than five year, 12.2 ng/ml in 5-9 yr, 6.7 ng/ml in 10-17 yr and 5.2 ng/ml in ≥18 yr. sIL2R accuracy to diagnose HLH marginally improved with age-appropriate cut-off. Interpretation & conclusions: Paediatric controls in India showed higher sIL2R levels than most studies conducted in other countries, except for some reports in Chinese and Russian populations. Age-appropriate reference values of sIL2R in a specific population may be considered to determine elevated sIL2R as a marker of HLH.

Atomic-resolution crystal structures of the immune protein conglutinin from cow reveal specific interactions of its binding site with N-acetylglucosamine.

Bovine conglutinin is an immune protein that is involved in host resistance to microbes and parasites and interacts with complement component iC3b, agglutinates erythrocytes, and neutralizes influenza A virus. Here, we determined the high-resolution (0.97-1.46 Å) crystal structures with and without bound ligand of a recombinant fragment of conglutinin's C-terminal carbohydrate-recognition domain (CRD). The structures disclosed that the high-affinity ligand N-acetyl-d-glucosamine (GlcNAc) binds in the collectin CRD calcium site by interacting with the O3' and O4' hydroxyls alongside additional specific interactions of the N-acetyl group oxygen and nitrogen with Lys-343 and Asp-320, respectively. These residues, unique to conglutinin and differing both in sequence and in location from those in other collectins, result in specific, high-affinity binding for GlcNAc. The binding pocket flanking residue Val-339, unlike the equivalent Arg-343 in the homologous human surfactant protein D, is sufficiently small to allow conglutinin Lys-343 access to the bound ligand, whereas Asp-320 lies in an extended loop proximal to the ligand-binding site and bounded at both ends by conserved residues that coordinate to both calcium and ligand. This loop becomes ordered on ligand binding. The electron density revealed both α and ß anomers of GlcNAc, consistent with the added α/ßGlcNAc mixture. Crystals soaked with α1-2 mannobiose, a putative component of iC3b, reported to bind to conglutinin, failed to reveal bound ligand, suggesting a requirement for presentation of mannobiose as part of an extended physiological ligand. These results reveal a highly specific GlcNAc-binding pocket in conglutinin and a novel collectin mode of carbohydrate recognition.

Infantile Achalasia Cardia.

BACKGROUND: Achalasia is extremely rare in infants. CASE CHARACTERISTICS: We report three infants of age 9, 7 and 12 months, who presented with recurrent non-bilious vomiting, repeated chest infection and severe failure to thrive. Diagnosis of achalasia cardia was confirmed on contrast-swallow study. Hellers cardiomyotomy with fundoplication led to complete symptomatic relief, and weight-gain on follow-up. MESSAGE: Achalasia cardia is often misdiagnosed as gastroesophageal reflux disease which leads to significant delay in diagnosis and increased morbidity.

Transilluminating testicular mass.

Testicular tumor in prepubertal age group is uncommon. Most of the testicular tumors are benign in this age group and present as painless, hard testicular mass. We present a case where a 7 year male child presented to us with painless scrotal swelling, which was cystic and transilluminating, clinically mimicking as hydrocele. On ultrasonography, the mass was solid. Orchidectomy was performed and histopathology revealed mature cystic teratoma.

Delayed presentation of hypertrophic pyloric stenosis: a rare case.

Hypertrophic pyloric stenosis (HPS) is the most common cause of gastric outlet obstruction in infants, with an incidence of 1.5 to 3 per 1000 live births, and classically presents at 3 to 4 weeks of age. Delayed presentation of HPS is an extremely rare occurrence after early infancy. With the exclusion of congenital HPS, gastric outlet obstruction in childhood is a rare condition (1:100,000). We report a case of delayed presentation of HPS in a 4 1/2-year-old child in whom the pylorus was hypertrophied and appeared like an "olive," and for which pyloromyotomy was curative.

Defining targets for complement components C4b and C3b on the pathogenic neisseriae.

Complement is a key arm of the innate immune defenses against the pathogenic neisseriae. We previously identified lipooligosaccharide on Neisseria meningitidis as an acceptor for complement C4b. Little is known about other neisserial targets for complement proteins C3 and C4, which covalently attach to bacterial surfaces and initiate opsonization and killing. In this study we demonstrate that Neisseria gonorrhoeae porin (Por) 1B selectively binds C4b via amide linkages and C3b via ester linkages. Using strains expressing hybrid Por1A/1B molecules, a region spanned by loops 4 and 5 of Por1B was identified as the preferred binding site for C4b. We also identified the opacity protein (Opa), a major adhesin of pathogenic neisseriae, as a target for C4b and C3b on both N. meningitidis and N. gonorrhoeae. Using N. gonorrhoeae variants that predominantly expressed individual Opa proteins, we found that all Opa proteins tested (A, B, C, D, E, F, and I) bound C4b and C3b via amide and ester linkages, respectively. Amide linkages with Por1B and Opa were confirmed using serum containing only the C4A isoform, which exclusively forms amide linkages with targets. While monomers and heterodimers of C4Ab were detected on bacterial targets, C4Bb appeared to preferentially participate in heterodimer (C5 convertase) formation. Our data provide another explanation for the enhanced serum sensitivity of Por1B-bearing gonococci. The binding of C3b and C4b to Opa provides a rationale for the recovery of predominantly "transparent" (Opa-negative) neisserial isolates from persons with invasive disease, where the bacteria encounter high levels of complement.

Embryonal rhabdomyosarcoma of the common bile duct.

A two-and half-year-old boy presented with a short history of fever, jaundice and abdominal distension. At laparotomy, a rhabdomyosarcoma (RMS) arising from the common bile duct (CBD) was found. The tumor including the CBD was successfully excised and a Roux-en-Y hepaticodochojejunostomy was performed. Postoperatively, the child received chemotherapy and is doing well on one-year follow-up the recent literature on the subject is reviewed.

Congenital pouch colon: Massive redilatation of the tubularized colonic pouch after pull-through surgery.

BACKGROUND/PURPOSE: Children with a type I/II congenital pouch colon (CPC) malformation associated with imperforate anus usually are treated by subtotal excision of the colonic pouch, tubularization of the remaining portion, and pull-through of the tubularized colon during definitive surgery. The authors report 3 patients treated in this fashion who presented 2 to 10(1/2) years later with massive redilatation of the previously tubularized colon and enterocolitis METHODS: There were no anal strictures or malpositioning of the pulled through bowel. Contrast enema showed massive redilatation of the colonic pouch. Near-total excision of the redilated pouch with anastomosis of normal proximal ileum/colon with the retained distal portion of the pouch was performed by the abdominal approach. RESULTS: Anastomotic leaks occurred in 2 patients but were treated successfully. Postoperatively, the patients had relief from their abdominal symptoms and improvement in fecal continence. CONCLUSIONS: The colonic pouch in CPC has a marked tendency to undergo redilatation, even after tubularization. The surgical procedure described here for the treatment of these patients appears to be satisfactory.