Defining Clinical and Immunological Predictors of Poor Immune Responses to COVID-19 mRNA Vaccines in Patients with Primary Antibody Deficiency

Journal of Clinical Immunology - Immune responses to coronavirus disease 2019 (COVID-19) mRNA vaccines in primary antibody deficiencies (PADs) are largely unknown. We investigated antibody and CD4+...     

Inflammatory bowel disease in children 5 years of age and younger

OBJECTIVES: Clinicians are becoming increasingly aware that inflammatory bowel disease (IBD) can affect all age groups, although it has not been well described in infants and young children. Our aim was to evaluate early onset IBD in patients 5 yr of age and younger. METHODS: Medical records of patients diagnosed with early onset IBD at The Children's Hospital of Philadelphia between 1977 and 2000 were reviewed. Patients were divided into three categories: those with Crohn's disease (CD), those with ulcerative colitis (UC), and those with indeterminant colitis (IC). RESULTS: A total of 82 patients fulfilled the criteria. In 12 patients (15%), the IBD diagnosis was changed during the course of illness. At the end of the follow-up period, linear growth failure was present in 10 of 35 (29%) children with CD, one of 30 (3%) with UC, and three of 17 (18%) with IC. Failure to thrive was a frequent presenting symptom in children with CD (44%) and IC (39%), whereas in all four patients with UC and failure to thrive the diagnosis was subsequently changed to CD or IC. A high proportion of patients with CD had large bowel (89%), and perianal (34%) disease. None of the tested patients were positive for anti-Saccharomyces cerevisiae antibody (ASCA), and 10 tested positive for perinuclear antineutrophil cytoplasmic antibody (three of five patients with CD, five of seven with UC, and two of three with IC). CONCLUSIONS: Failure to thrive, at the time of presentation, is indicative of a final diagnosis of CD or IC, not UC. Linear growth failure is a common finding in patients with early onset CD. A high proportion of patients with CD have failure to thrive, colonic, and perianal disease. The IBD serology panel is of limited clinical relevance in providing definitive diagnostic information in this pediatric population.     

Endoscopic electronic medical record systems

EEMR systems have become an integral part of the daily operation of many endoscopy units. Systems have evolved from simple endoscopy report generators to sophisticated endoscopy unit managers. Newer features of these systems may improve patient care and enhance endoscopy unit efficiency and productivity, but further studies are needed. The needs of the endoscopy unit, the staff, and the endoscopist should drive the selection process when choosing an EEMR. Extensive testing of the EEMR system capabilities, especially the ability to interface with existing software programs, is essential before purchasing an EEMR system.     

An immunological determinant of RNase P protein is conserved between Escherichia coli and humans.

RNase P, an enzyme with RNA and protein subunits, cleaves tRNA precursor molecules to form the 5' termini of mature tRNAs in both prokaryotes and eukaryotes. Rabbit antibodies made against the protein subunit, C5 protein, of Escherichia coli RNase P bound RNase P protein from E. coli and Bacillus subtilis in immunoblots and solid-phase immunoassays. These rabbit anti-C5 antibodies also bound a protein (Mr approximately 40,000) in preparations of RNase P from human (HeLa) cells and depleted the enzymatic activity from preparations of RNase P from both human and E. coli cells. Finally, rabbit anti-C5 antibodies immunoprecipitated from crude extracts of human cells a ribonucleoprotein complex containing H1 RNA, the putative RNA component of human RNase P. These results show that an antigenic determinant is shared by C5 protein from E. coli RNase P and a protein component of RNase P from human cells.     

Treatment of iron deficiency anemia in pediatric inflammatory bowel disease

Opinion statement Anemia is a frequent extraintestinal manifestation of inflammatory bowel disease (IBD) that is commonly overlooked, despite its significant impact on quality of life. Characteristic symptoms include chronic fatigue, headache, and subtle impairment of cognitive function, although some less common symptoms include dyspnea, dizziness, pica, angular stomatitis, shortened attention span, and esophageal webs. Several types of anemia are associated with IBD, but iron deficiency anemia (IDA) accounts for the majority of cases and others include anemia of chronic disease, anemia associated with vitamin deficiency (vitamin B₁₂ and folate), autoimmune anemia, and anemia caused by medication used to treat IBD. The diagnosis of IDA relies on laboratory blood tests. Therefore, these tests should be obtained on a regular basis because characteristic symptoms may be absent or not readily recognized by patients and their clinicians. Complete blood count may suffice; however, iron studies and serum vitamin levels may be necessary to differentiate between specific types of anemia. During the diagnostic process, it is important to consider coexistence of different types of anemia, especially if no response to therapy is noted. The therapy for anemia is directed towards treatment of the underlying inflammatory process and supplemental therapy, depending on the type of deficiency. Iron deficiency anemia is treated with iron preparations, first orally, and if unresponsive or if associated with untoward adverse events leading to decrease in adherence with the therapeutic regimen, with intravenous preparations. Intramuscular therapy has been abandoned due to high rate of complications. Intravenous therapy may be administered as a multiple-dose regimen (intravenous iron sucrose and gluconate) or as a single intravenous dose (iron dextran), which is associated with a higher risk of allergic infusion reactions and requires obligatory test dose administration. Treatment with erythropoietin is reserved for a select subgroup of patients with anemia of chronic disease. With appropriate treatment, the majority of patients with IBD will have significant improvement or resolution of anemia, which can lead to a better quality of life. However, a high index of suspicion should be maintained in order to identify the precise cause of anemia and to prescribe the appropriate therapy.     

Experimental Autoimmune Encephalomyelitis in the Wistar Rat: Dependence of MBP-specific T Cell Responsiveness on B7 Costimulation

Experimental autoimmune encephalomyelitis (EAE) is an animal model of human multiple sclerosis that requires the activation of autoreactive T cells for the expression of pathology. EAE has been most frequently studied in the Lewis rat model as well as in several murine models of EAE including the PLJ and B10PL strains. In the present study we describe a novel model of EAE induced in the Wistar rat strain by immunization with guinea pig spinal cord antigens and pertussis toxin (PT). T cell responses were induced to myelin basic protein. Autoreactive T cells could be totally blocked by the in vitro treatment with CTLA4Ig, a protein that blocks the costimulation of autoreactive T cells. The addition of IL-2 could reverse the inhibition seen in vitro with CTLA4Ig. The effects of inhibition of B7 costimulation were also examined by an analysis of cytokine responses and IL-2 receptor on T cells. CTLA4Ig treatment in vitro reduced the expression of IL-2 receptor on T cells, enhanced T cell apoptosis and decreased the synthesis of IL-2, IFN- &#110 and TNF- &#102 . CTLA4Ig treatment had no effect on IL-10 synthesis by T cells, a cytokine implicated in the functions of regulatory T cell subsets. Overall, our studies support the rationale of B7 blocking therapies as a potential treatment for models of multiple sclerosis. The induction of EAE in the Wistar rat provides yet another novel model in which to examine the regulation of T cell autoimmunity.     

snRNPs and scRNPs as autoantigens: clues to the etiology of the connective tissue diseases

Clinical Rheumatology -     

Return on investment imperative: the cost of care calculator for an evidence-based practice program

The key elements of the evaluation process of an evidence-based practice (EBP) program and the infrastructure needed as identified by a large health care organization. The EBP evaluation program has 2 major elements for measuring success. The first component for evaluation is the impact on the clinical outcomes of care and the second is the fiscal implications of implementing the EBP. This article focuses on the fiscal evaluation component and describes a process to calculate the cost of care compared to before and after implementation of the EBP. The literature to support the care calculations is examined and a cost algorithm is described.     

Induction of autoreactive B cells allows priming of autoreactive T cells

A novel mechanism for breaking T cell self tolerance is described. B cells induced to make autoantibody by immunization of mice with the non-self protein human cytochrome c can present the self protein mouse cytochrome c to autoreactive T cells in immunogenic form. This mechanism of breaking T cell self tolerance could account for the role of foreign antigens in breaking not only B cell but also T cell self tolerance, leading to sustained autoantibody production in the absence of the foreign antigen.     

Management of ingested magnets in children

ABSTRACT: We describe a comprehensive algorithm for the management of ingested rare-earth magnets in children. These newer and smaller neodymium magnets sold as adult toys are much stronger than the traditional magnets, and can attract each other with formidable forces. If >1 magnet is swallowed at the same time, or a magnet is co-ingested with another metallic object, the loops of intestine can be squeezed between them resulting in bowel damage including perforations. An algorithm that uses the number of magnets ingested, location of magnets, and the timing of ingestion before intervention helps to delineate the roles of the pediatric gastroenterologists and surgeons in the management of these cases.