Correction to: Impact of smoking habit on adult-onset Still’s disease prognosis,findings from a multicentre observational study

Clinical Rheumatology -     

Human CD4 “internal antigen” mimicry by anti-idiotypic monoclonal antibodies

Summary Of 1019 hybridomas generated from a BALB/c mouse immunized with the syngeneic anti-CD4 monoclonal antibody HP2/6, 3 were found to secrete anti-idiotypic antibodies. Detailed analysis of anti-idiotypic monoclonal antibodies F16-10F6, F16-14D6 and F16-16D7 showed they recognize idiotope(s) not expressed by any of the anti-CD4 monoclonal antibodies tested, including those which inhibit the binding of HP2/6 to CD4 antigen. The idiotope recognized by the three anti-idiotypic antibodies are within (or closely related to) the antigen combining site of the immunizing antibody and distinct and spatially distant from the idiotope defined by monoclonal antibody F11-2302 which was previously shown to be outside the antigen combining site of HP2/6. Although F16-14D6 and F16-16D7 are indistinguishable in isotype, binding titer to idiotopes, fine specificity on a panel of monoclonal antibodies, relation to the combining site and competitive binding, it is likely that they are structurally different and recognize two distinct combining site-related idiotopes on HP2/6, as they display different spectrotypes and induce antianti-idiotypic (Ab3) immune sera with different specificities. Analysis of the fine specificity of the two Ab3 immune sera suggest they share idiotopes with HP2/6 and contain antibodies reacting with CD4 antigen. Among the latter, those induced with F16-14D6 display a different CD4 epitope specificity than HP2/6. Hence, anti-idiotypic antibodies F16-14D6 and F16-16D7 behave as “network antigen” for human CD4; idiotope-triggered antibody cascade may have a role in changing the specificities of antibody.     

Calciphylaxis in a patient with POEMS syndrome without renal failure and/or hyperparathyroidism. A case report

POEMS (Crow-Fukase) syndrome is a rare plasma cell lymphoproliferative disorder associated with polyneuropathy (P), organomegaly (O), endocrinopathy (E), monoclonal (M) gammopathy and skin (S) abnormalities. The latter are usually not specific and include hyperpigmentation, hypertrichosis, cutaneous angioma and skin-thickening. A 45-year-old Italian woman was admitted to hospital because of muscle weakness, marked fatigue and paresthesia of the upper and lower extremities. Two and a half years earlier, a POEMS syndrome had been diagnosed on the basis of a history of organomegaly and mild lymphadenopathy, IgA-lambda monoclonal gammopathy, hypothyroidism, severe lower and upper limb sensory-motor peripheral neuropathy and a single osteosclerotic lesion in the left humerus. Eight weeks later, she developed skin lesions bioptically shown to be due to calciphylaxis-induced cutaneous vasculitis. To our knowledge, this is the first case of POEMS syndrome with this peculiar type of vasculitis. The absence of predisposing conditions, namely renal failure, hyperparathyroidism or clotting disorders renders the pathogenetic mechanism(s) of this severe type of vasculitis more intriguing.     

Comparison of the direct fluorescence assay and real-time polymerase chain reaction for the detection of influenza virus A and B in immunocompromised patients

OBJECTIVE:

This study evaluated the diagnostic performance of two methods for the detection of influenza virus in immunocompromised transplant patients.

METHODS:

A total of 475 respiratory samples, 236 from patients in a hematopoietic stem cell transplantation program and 239 from kidney transplant patients, were analyzed by a direct fluorescence assay and the Centers for Disease Control real-time polymerase chain reaction protocol for influenza A and B detection.

RESULTS:

Influenza detection using either method was 7.6% in the hematopoietic stem cell transplant group and 30.5% in the kidney transplant patient group. Influenza detection by real-time polymerase chain reaction yielded a higher positive rate compared with fluorescence than that reported by other studies, and this difference was more pronounced for influenza A. The fluorescence assay sensitivity, specificity, positive and negative predictive values, and kappa coefficient were 17.6%, 100%, 1, 0.83, and 0.256, respectively, and lower detection rates occurred in the kidney transplant patients.

CONCLUSIONS:

The real-time polymerase chain reaction performance and the associated turnaround time for a large number of samples support the choice of this method for use in different routine diagnostic settings and influenza surveillance in high-risk patients.     

Murine antiidiotypic monoclonal antibodies that bear the internal image of HLA-DR allospecificities

Hybridization of murine myeloma cells P3-X63-Ag8.653 with splenocytes from a BALB/c mouse immunized with the syngeneic anti HLA-DR1,4,w6,w8,w9 MAb AC1.59 resulted in the development of 108 hybridomas secreting antiidiotypic antibodies. 100 of them inhibited the binding of MAb AC1.59 to target cells. Detailed analysis of the antiidiotypic MAb F5-444, F5-830, F5-963, F5-1126, F5-1336, and F5-1419 showed that all of them recognize idiotopes within or spatially close to the antigen combining site of MAb AC1.59. In cross-blocking experiments, the six antiidiotypic MAbs cross-blocked each other. It is likely that the six MAbs recognize spatially close, but not identical idiotopes because they elicited antiantiidiotypic antibodies of different or similar, but not identical specificity and differ in their ability to elicit anti-HLA class II antibodies. The latter, which were found only in sera from BALB/c mice immunized with antiidiotypic MAb F5-444 and F5-830, mimic the specificity of MAb AC1.59 and express the idiotope defined by the immunizing antiidiotypic MAb. These results indicate that the MAb F5-444 and F5-830 are antiidiotypes beta and the remaining four are antiidiotypes gamma.     

Rapid assessment of influenza vaccine effectiveness: analysis of an internet-based cohort

The effectiveness of influenza vaccination programmes is seldom known during an epidemic. We developed an internet-based system to record influenza-like symptoms and response to infection in a participating cohort. Using self-reports of influenza-like symptoms and of influenza vaccine history and uptake, we estimated vaccine effectiveness (VE) without the need for individuals to seek healthcare. We found that vaccination with the 2010 seasonal influenza vaccine was significantly protective against influenza-like illness (ILI) during the 2010-2011 influenza season (VE 52%, 95% CI 27-68). VE for individuals who received both the 2010 seasonal and 2009 pandemic influenza vaccines was 59% (95% CI 27-77), slightly higher than VE for those vaccinated in 2010 alone (VE 46%, 95% CI 9-68). Vaccinated individuals with ILI reported taking less time off work than unvaccinated individuals with ILI (3.4 days vs. 5.3 days, P<0.001).     

Impact of Cold Ischemia Time on the Function of Liver Grafts Preserved With Custodiol

ObjectiveThis study aimed to evaluate how cold ischemia time (CIT) interferes with liver graft function in the first 7 days after surgery for Custodiol (HTK) preserved organs.MethodsThis retrospective observational study analyzed the medical records of 38 transplantation patients at Hospital Leforte Liberdade, São Paulo, in 2018. The study population was divided into 2 groups (group A, CIT < 8 hours; group B, CIT > 8 hours). Postoperative parameters—such as international normalized ratio, total bilirubin, aspartate aminotransferase/alanine aminotransferase, alkaline phosphatase, gamma glutamyl transferase (GGT), lactate dehydrogenase, lactate, creatinine, red blood cell transfusion, need for hemodialysis, use of vasoactive drugs, endotracheal intubation time, length of stay in the intensive care unit (ICU), and length of hospital stay—were compared.ResultsGroup A (CIT < 8 hours) presented less need for red blood cell transfusions (odds ratio 0.29; confidence interval 0.06-0.98; P = .04), had a shorter hospital stay (P = .024), and had lower levels of total bilirubin (P = .05) and GGT (P = .05) in the first 7 postoperative days. The other variables showed no statistically significant difference.ConclusionIn livers preserved with Custodiol, CIT > 8 hours generated higher levels of total bilirubin and GGT in the postoperative period, in addition to higher hospital costs; greater need for red blood cell transfusions; and longer hospitalization, including longer stays in the ICU.     

500 Consecutive Liver Transplants: The Outcomes of a New Transplantation Program in the Middle West of Brazil

IntroductionLiver transplantation is the standard treatment for end-stage liver disease. Brazil holds the third highest number of liver transplants performed per year, but center maldistribution results in high discrepancies in accessing this treatment. In 2012, an interstate partnership successfully implemented a new liver transplantation program in the middle west of Brazil. Here, we report the results of the first 500 liver transplants performed in this new program and discuss the impacts of a new transplant center in regional transplantation dynamics.MethodsWe reviewed data from the first 500 consecutive deceased donor liver transplants performed in the new program during an 8-year period. We analyzed data on patients’ clinical and demographic profiles, postoperative outcomes, and graft and recipient survival rates. Univariate survival analysis was conducted using log-rank tests to compare the groups.ResultsAlmost half (48%) of the procured organs and 40% of the recipients transplanted in our center were from outside our state. Recipient 30-day mortality was 9%. Overall recipient survival at 1 year and 5 years was 85% and 80%, respectively. Mortality was significantly associated with higher Model for End-Stage Liver Disease (P < .001) but not with the presence of hepatocellular carcinoma (P = .795).DiscussionThe new transplantation program treated patients from different regions of Brazil and became the reference center in liver transplantation for the middle west region. Despite the recent implementation, our outcomes are comparable to experienced centers around the world. This model can inspire the creation of new transplantation programs aiming to democratize access to liver transplantation nationwide.     

Syngeneic antiidiotypic monoclonal antibodies to the murine anti-HLA-DR,DP monoclonal antibody CR11-462

Two out of 625 hybridomas constructed with splenocytes from a Balblc mouse immunized with the murine anti-HLA-DR, DP monoclonal antibody CR11-462 secrete antiidiotypic antibodies. Binding assays with a panel of 12 anti-HLA class I, 14 anti-HLA class II, and 9 anti-human melanoma-associated antigen MoAbs showed that the idiotopes recognized by MoAb F3-C25 and F3-B6 are not expressed by any of the tested antibodies, even those which inhibit the binding of MoAb CR11-462 to cultured B lymphoid cells. Crossblocking experiments showed that the two idiotypes are distinct and spatially distant. Both idiotopes require the association of heavy and light chain of MoAb CR11-462 for their expression. The idiotope recognized by MoAb F3-B6 is an idiotope, since it is located outside the antigen combining site of MoAb CR11-462. The idiotope recognized by MoAb F3-C25 is a γ idiotope, since it is antigen inhibitable but does not posses an internal image of the antigen. Interestingly the MoAb F3-C25 displays a differential inhibitory effect on the binding of MoAb CR11-462 to lymphoid cells that express different HLA phenotypes or share the HLA-DRw6 allospecificity. These results suggest that antiidiotypic antibodies may sharpen our ability to dissect the heterogeneity of HLA class II antigens.