Airway hyper-reactivity mediated by B-1 cell immunoglobulin M antibody generating complement C5a at 1 day post-immunization in a murine hapten model of non-atopic asthma

Contact skin immunization of mice with reactive hapten antigen and subsequent airway challenge with the same hapten induces immediate airflow obstruction and subsequent airway hyper‐reactivity (AHR) to methacholine challenge, which is dependent on B cells but not on T cells. This responsiveness to airway challenge with antigen is elicited as early as 1 day postimmunization and can be adoptively transferred to naïve recipients via 1‐day immune cells. Responses are absent in 1‐day immune B‐cell‐deficient JH^?/? mice and B‐1 B‐cell‐deficient xid male mice, as well as in recipients of 1‐day immune cells depleted of cells with the B‐1 cell phenotype (CD19⁺ B220⁺ CD5⁺). As B‐1 cells produce immunoglobulin M (IgM), we sought and found significantly increased numbers of anti‐hapten IgM‐producing cells in the spleen and lymph nodes of 1‐day immune wild‐type mice, but not in xid mice. Then, we passively immunized naive mice with anti‐hapten IgM monoclonal antibody and, following airway hapten challenge of the recipients, we showed both immediate airflow obstruction and AHR. In addition, AHR was absent in complement C5 and C5a receptor‐deficient mice. In summary, this study of the very early elicited phase of a hapten asthma model suggests, for the first time, a role of B‐1 cells in producing IgM to activate complement to rapidly mediate asthma airway reactivity only 1 day after immunization.     

Emergence of chronic Lyme arthritis: Putting the breaks on CD28 costimulation

Lyme disease is a debilitating infection that is caused upon a bite of Borrelia burgdorferi (Bb)-infected ticks. One of the most prominent clinical manifestations is the development of chronic Lyme arthritis. Months after Bb infection, ~60% of untreated Lyme patients experience intermittent arthritic attacks that may last for years. The use of the CD28^?/? mouse in Bb infection has helped to shed light into the mechanisms that govern this inflammatory process, which seems to be tightly regulated. In this current review, the effect of immunoregulation, as well as CD28 deficiency in the development of chronic Lyme arthritis is discussed.     

Pulp revascularization for immature replanted teeth: a case report

Immature avulsed teeth are not usually treated with pulp revascularization because of the possibility of complications. However, this therapy has shown success in the treatment of immature teeth with periapical lesions. This report describes the case of an immature replanted tooth that was successfully treated by pulp revascularization. An 8‐year‐old boy suffered avulsion on his maxillary left lateral incisor. The tooth showed incomplete root development and was replanted after 30 minutes. After diagnosis, revascularization therapy was performed by irrigating the root canal and applying a calcium hydroxide paste and 2% chlorhexidine gel for 21 days. In the second session, the intracanal dressing was removed and a blood clot was stimulated up to the cervical third of the root canal. Mineral trioxide aggregate was placed as a cervical barrier at the entrance of the root canal and the crown was restored. During the follow‐up period, periapical repair, apical closure and calcification in the apical 4 mm of the root canal was observed. An avulsed immature tooth replanted after a brief extra‐alveolar period and maintained in a viable storage medium may be treated with revascularization.     

Novel and recurrent germline LEMD3 mutations causing Buschke–Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis

Mutations in the LEMD3 gene were recently incriminated in Buschke–Ollendorff syndrome (BOS) and osteopoikilosis, with or without melorheostosis. The relationship of this gene with isolated sporadic melorheostosis is less clear. We investigated LEMD3 in a two-generation BOS family showing an extremely variable expression of the disease, in a sporadic patient with skin features of BOS, and in an additional subject with isolated melorheostosis. We identified two different mutations, both resulting in a premature stop codon, in the two cases of BOS. The mutation (c.2564G>A) reported in the familial case is novel, while that observed in the sporadic case (c.1963C>T) has been previously reported in an American woman with osteopoikilosis and melorheostosis who had a family history of isolated osteopoikilosis. The search for mutations in DNA extracted from the peripheral blood, as well as skin and bone biopsies of the patient with melorheostosis failed to identify any pathogenic change. Our results further expand the LEMD3 mutation repertoire, corroborate the extreme interfamilial and intrafamilial clinical variability of LEMD3 mutations, and underline the lack of a clear phenotype–genotype correlation in BOS. The present study supports the general conclusion that LEMD3 mutations do not contribute to isolated sporadic melorheostosis. The genetic or epigenetic influences that are responsible for the development of melorheostosis require further investigation.     

Less severe retinopathy of prematurity induced by surfactant replacement therapy

To assess the effect of surfactant replacement therapy (SRT) on the prevalence and severity of retinopathy of prematurity (ROP), we compared data from 160 SRT-treated preterm infants with data from 230 historic controls. The prevalence of ROP was 30.6% in the treatment group and 23.4% in the control group. Severe ROP (stages 3-4) was seen in 6.1% of the infants with ROP in the treatment group and 20.3% of the ROP patients in the control group. Surfactant therapy had no influence on the prevalence of ROP (odds ratio 1.4, 95% confidence interval 0.797-2.459, p = 0.242). However, SRT was associated with a decreased risk for severe ROP, compared to mild ROP (odds ratio 0.226, 95% confidence interval 0.056-0.905, p = 0.036). These data suggest that SRT is associated with a decreased risk for severe ROP.     

Leukocytoclastic Vasculitis: Is Propranolol Implicated?

Drugs frequently cause cutaneous adverse reactions. The suspected agent is sometimes difficult to identify, especially in patients receiving multidrug treatment and with underlying illnesses that may contribute to the clinical picture. In our patient, propranolol-induced leukocytoclastic vasculitis was diagnosed by exclusion.