MyD88 in osteoclast- and osteoblast-lineages differentially controls bone remodeling in homeostasis and malaria.

Chronic bone loss is an under-recognized complication of malaria, the underlying mechanism of which remains incompletely understood. We have previously shown that persistent accumulation of Plasmodium products in the bone marrow leads to chronic inflammation in osteoblast (OB) and osteoclast (OC) precursors causing bone loss through MyD88, an adaptor molecule for diverse inflammatory signals. However, the specific contribution of MyD88 signaling in OB or OC precursors in malaria-induced bone loss remains elusive. To assess the direct cell-intrinsic role of MyD88 signaling in adult bone metabolism under physiological and infection conditions, we used the Lox-Cre system to specifically deplete MyD88 in the OB or OC lineages. Mice lacking MyD88 primarily in the maturing OBs showed a comparable decrease in trabecular bone density by microcomputed tomography (µCT) to that of controls after PyNL infection. In contrast, mice lacking MyD88 in OC precursors showed significantly less trabecular bone loss than controls, suggesting that malaria-mediated inflammatory mediators are primarily controlled by MyD88 in the OC lineage. Surprisingly, however, depletion of MyD88 in OB, but not in OC precursors, resulted in reduced bone mass with decreased bone formation rates in the trabecular areas of femurs under physiological conditions. Notably, IGF-1, a key molecule for OB differentiation, was significantly lower locally and systemically when MyD88 was depleted in OBs. Thus, our data demonstrate an indispensable intrinsic role for MyD88 signaling in OB differentiation and bone formation, while MyD88 signaling in OC lineages plays a partial role in controlling malaria-induced inflammatory mediators and following bone pathology. These findings may lead to the identification of novel targets for specific intervention of bone pathologies, particularly in malaria-endemic regions.

Selective IgM deficiency: Follow-up and outcome.

BACKGROUND: Selective IgM deficiency (sIgMD) is classified under primary immunodeficiencies (PID). This study aimed to define the clinical and immunologic features of sIgMD. PATIENT AND METHODS: We assessed a retrospective medical record of patients who fulfilled the diagnostic criteria for sIgMD in a pediatric immunology department. RESULTS: There were 55 patients with sIgMD. Out of 55 patients, 13 (23.6%) patients, diagnosed with a well-defined PID disease, and nine, evaluated as transient hypogammaglobulinemia, were excluded in the follow-up. The ratio of the sIgMD was %0.12 in the outpatient clinic of pediatric immunology (33/27,000). Out of 33 patients, eight (24,2%) were asymptomatic during the follow-up period. Fifteen (45.4%) patients presented with upper/lower respiratory and skin infections. Six patients (18%) had chromosomal anomaly, or syndrome (trisomy 21, 22q11.2 deletion 1p deletion, CHARGE syndrome, and Cohen syndrome). Six (18%) had autoimmune/inflammatory diseases, such as Behcet's disease, immune thrombocytopenic purpura, Crohn's disease, Guillain-Barre syndrome, and diabetes mellitus. Five (15%) had allergic disorders. Three patients (9%) developed malignancy. The PID diagnoses were combined immunodeficiency, common variable immunodeficiency, chronic granulomatous disease, adenosine deaminase deficiency, and congenital neutropenia. CONCLUSION: Genetic disorders, autoimmune/inflammatory, and allergic diseases may accompany sIgMD. Approximately 25% of the patients were asymptomatic in our series. Patients had increased malignancy risk. We diagnosed about 25% of the patients having low IgM with a specific PID in the follow-up period. Thus, patients with sIgMD should be followed up regularly in immunology clinics.

Myocarditis associated with influenza infection in five children.

BACKGROUND: Myocarditis is an inflammatory condition located mainly in the myocardium. It is caused by a variety of bacterial and viral infections. Influenza is one of the most common relevant viruses that cause myocarditis. OBJECTIVES: We attempted to share our experiences about clinical and laboratory findings, cardiac evaluation, and treatment of children with influenza myocarditis. METHODS: This retrospective study was performed by the Department of Pediatric Infectious Diseases at the Faculty of Medicine, Hacettepe University in Turkey. The medical records of patients diagnosed with myocarditis associated with an influenza infection between January 2014 and January 2017 were systematically reviewed. RESULTS: Vaccination seems likely to be an important protection strategy for both influenza infections and complications.