Objective. CD22 is a surface molecule exclusively expressed on B cells that regulates adhesion and B cell receptor (BCR) signaling as an inhibitory coreceptor of the BCR. Central downstream signaling molecules that are activated upon BCR engagement include spleen tyrosine kinase (Syk) and, subsequently, phospholipase C␥2 (PLC␥2), which results in calcium (Ca 2؉ ) mobilization. The humanized anti-CD22 monoclonal antibody epratuzumab is currently being tested in clinical trials. This study was undertaken to determine the potential mechanism by which this drug regulates B cell activation.Methods. Purified B cells were preincubated with epratuzumab, and the colocalization of CD22 and CD79␣, without BCR engagement, was assessed by confocal microscopy. Conclusion. These findings are consistent with the concept of targeting CD22 to raise the threshold of BCR activation, which could offer therapeutic benefit in patients with autoimmune diseases.Antigen binding to the cognate B cell receptor (BCR) induces intracellular activation signals, usually resulting in differentiation, proliferation, or, alternatively, apoptosis of B cells. An intact BCR is a requirement for differentiation of naive and, in part, memory B cells into plasma cells, based on BCR engagement together with costimulatory activation. This pathway also results in immunoglobulin class switching and somatic hypermutation, characteristics known to establish B cell memory. Furthermore, an intact antigen receptor signal is an essential precondition for B cell maturation from pre-B cells to the immature stage, and for the survival of mature B cells (1,2).CD22 is an inhibitory coreceptor of the BCR that is exclusively expressed on B cells (3). It plays a key role in setting the threshold of the BCR response (3-5). Engagement of CD22 initiates its phosphorylation, which subsequently activates SH2 domain-containing protein tyrosine phosphatase 1 (SHP-1) and leads to attenuation of BCR signaling via dephosphorylation of Supported by the DFG (Collaborative Research Centre grant 650/TP16 and DFG grant 491/7-1) and in part by UCB

BackgroundAcute focal bacterial nephritis (AFBN) is a rare disease currently described only in case reports and small case series. In this study we summarize the clinical features of AFBN as has been documented in the literature and draw recommendations on the proper diagnosis and therapy.MethodsA systematic literature review was undertaken in PUBMED, Web of Science and The Cochrane Library online databases for relevant literature on AFBN in adults.ResultsLiterature review revealed a total of 38 articles according to our inclusion criteria, of which we could extract data from 138 cases of AFBN. Fever (98%) and flank pain (80%) were most commonly reported symptoms. E. coli was the most frequent pathogen. Diagnosis was set by CT and/or MRI (52%) with or without sonography or by sonography alone (20%) as well as by sonography combined with IVU. In total, sonography was applied in 83% of cases. All but one patient received antibiotic treatment. Kidney lesions were occasionally mistaken for neoplasms or renal abscesses and as a result, cases were subjected to percutaneous puncture (12.3%), surgical exploration (5.1%) and partial or radical nephrectomy (4.4%). Four cases (2.9%) developed a renal abscess.ConclusionsThe diagnosis of AFBN is set by characteristic clinico-radiological findings. Differential diagnoses of this interstitial bacterial infection include renal abscess and tumor. Correct diagnosis is occasionally impeded by atypical symptoms. Invasive diagnostic and therapeutic procedures should be limited as the majority of cases respond well to conservative treatment.

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Acute focal bacterial nephritis (AFBN) is a rarely diagnosed interstitial bacterial infection of the kidney. Due to the non-specific clinical presentation of this entity, correct diagnosis can be challenging. In this work, we present three cases of AFBN aiming to stress the diversity of clinical presentation associated with the disease and the fact that patients with AFBN are at risk of undergoing unnecessary invasive procedures. The employment of invasive diagnostic and therapeutic procedures on the management of AFBN should be limited, as the majority of patients respond well to conservative therapy.