Abstract Background/Aims Pneumococcal pneumonia is an important cause of morbidity and mortality amongst patients with inflammatory arthritis. Vaccination is recommended by the National Institute of Clinical Excellence (NICE) but it remains unclear how vaccine efficacy is impacted by different immunosuppressive agents. Our objective was to compare the chance of a seroconversion following vaccination against pneumococcus in patients with inflammatory arthritis to the general population as well as to compare the chance of seroconversion across different targeted therapies. Methods We searched MEDLINE, Embase and the Cochrane library databases from inception until 20th June 2023. We included randomised controlled trials and observational studies. Aggregate data were used to undertake pairwise meta-analysis. Our primary outcome of interest was vaccine seroconversion. We accepted the definition of serological response reported by the authors of each study. Results 20 studies identified in the systematic review (2,807 patients) with 10 reporting sufficient data to be included in the meta-analysis (1,443 patients). The odds of seroconversion in patients receiving targeted therapies, relative to the general population, was 0.61 (95% CI 0.35 to 1.08). The reduced odds of response was skewed strongly by the effects of abatacept and rituximab with no difference between patients on TNF inhibitors or IL6 inhibition and healthy controls. In the analysis comparing within inflammatory arthritis populations the findings remained consistent with rituximab having the strongest negative impact on vaccine response. TNF inhibition monotherapy associated with a greater odds of vaccine response compared with methotrexate (2.25 (95% CI 1.28 to 3.96)). JAK inhibitor studies were few in number and did not present comparable vaccine response endpoints to include in meta-analysis. The information available does not suggest a significant detrimental effects of JAK inhibitor on vaccine response. Conclusion This updated meta-analysis confirms that for the majority of patients with inflammatory arthritis, pneumococcal vaccine can be administered with confidence that it will achieve comparable seroconversion rates to the healthy population. Patients on rituximab were the group least likely to achieve a response and further research is needed to explore the value of multiple course pneumococcal vaccination schedules in this population. Disclosure D. Nagra: Honoraria; Abbvie, Galapagos, UCB. K. Bechman: None. M. Adas: None. Z. yang: None. E. Alveyn: None. S. Patel: None. M. Russell: None. S. Norton: None. C. Wincup: None. C. Baldwin: None. J. Galloway: None.
BACKGROUND: A “BeadChip” array permits reliable simultaneous DNA typing of single‐nucleotide polymorphisms for minor blood groups. A high‐throughput DNA analysis was studied as a routine method of phenotype prediction and software was developed to interpret and analyze the large volume of data points. STUDY DESIGN AND METHODS: DNA was extracted from whole blood of donors of known phenotypes and self‐identified ethnicity. Analysis of single‐nucleotide polymorphisms (SNPs) associated with 24 antigens of 10 blood group systems was performed with BeadChips (BioArray Solutions), and the results were compared to historical serologic typings. Phenotypes were predicted for individual samples, and phenotype prevalence was determined for ethnicities. The BeadChip was expanded to incorporate SNPs that silence the S antigen, validated, and tested with 369 DNA samples. A time‐motion analysis was conducted. RESULTS: Results of BeadChip analyses were concordant with prediction of antigen negativity for 4,510 antigens. Eight discordant results were due to silencing of GYPB S and 16 were likely errors in recording serological results or data entry. The analyses produced 19,457 antigen‐negative typings not serologically defined, identified 21 rare donors (Co(a–b+) [n = 1], Jo(a–) [n = 6], S–s–[n = 12], and K+k–[n = 2]), and determined allele frequencies and antigen prevalence for four ethnicities. The expanded panel detected 30 SS, 235 ss, 100 Ss, and 4 U– samples. The format processes 192 DNA samples (two plates) per 8‐hour shift per technician, including automated data analysis and report generation. CONCLUSION: DNA analysis with BeadChip format, combined with computerized data entry and analysis, permits the prediction of minor blood group antigens.
Vaccination against pneumococcus reduces the risk of infective events, hospitalisation, and death in individual with inflammatory arthritis, particularly in those on immunomodulating therapy who are at risk of worse outcomes from pneumococcal disease. The objective of this study was to investigate the serological protection following vaccination against pneumococcal serovars over time.
Abstract Introduction Sarcoidosis affects approximately 1% of the population. There are two situations where it came become life threatening: seizures secondary to neuro-sarcoidosis and arrhythmias due to cardiac infiltration. Currently there are limited licenced therapies for the treatment of sarcoidosis. We describe a case of cutaneous and neuro-sarcoidosis who developed subsequent multi-system sarcoidosis. Case description A previously fit and well 50-year-old presented to his local hospital with tonic clonic seizures. He worked as a mortgage broker and never smoked. There was no pro-drome and on examination it was noted he had erythema nodosum on his shins. He was investigated with a CT head and subsequent MRI demonstrating enhancement of his leptomeninges, mid brain parenchyma, hypothalamus and pituitary gland. A lumbar puncture was performed with an elevated protein level of 934g with a normal glucose and lymphocyte level. The CSF was negative for TB. A CT of his chest was performed demonstrating bilateral hilar lymphadenopathy and subsequent histology of these lymph nodes demonstrated non-necrotising, non-caseating epithelioid granulomas. A diagnosis of sarcoidosis was made and he was commenced on mycophenolate. His disease remained quiescent for 5 years before the eruption of further skin lesions. He developed multiple subdermal nodules on his fingers, wrists, elbows which were biopsied demonstrating cutaneous sarcoidosis. Neurological examination demonstrated brisk lower limb reflexes with upgoing plantars. He was commenced on a tapering course of prednisolone and an evaluation for extra-cutaneous disease was made. An IL2Ra was 4719ng/L (423-1843) with a normal ACE. Pituitary axis testing revealed a slightly raised prolactin (326 mIU/L). A CT-PET was performed demonstrating extensive metabolic activity in his skin, central nervous system, liver, spleen, salivary glands, skeletal uptake in both humeral heads alongside myocardial uptake. An urgent cardiac MRI was performed demonstrating active myocardial disease. An ECG did not demonstrate any conduction abnormalities. A diagnosis of multi-system sarcoidosis was made warranting an urgent MDT discussion given the progression of his disease. Discussion In this particular case, it had been assumed that his sarcoidosis was inactive until the emergence of the skin lesions. It was the skin lesions that lead to an assessment for multi-system sarcoidosis. It is common for the serum ACE level to be normal, as seen in up to 50% of cases and it was the Il2Ra elevation that prompted the CT-PET request. Given the extent and progression of disease despite treatment with mycophenolate, this gentlemen was given a tapering regime of prednisolone (starting at 20mg) and his mycophenolate was switched to methotrexate which has shown to have superior efficacy to mycophenolate for sarcoidosis. Furthermore, infliximab at a dose of 5mg/kg was commenced shortly after to control the increasing CNS lesions. Infliximab is a well recognised treatment for sarcoidosis; however, due to limited clinical trial data, it remains unlicenced for use in sarcoidosis with the exception of neuro-sarcoidosis (following the failure of DMARD therapy). To date, the patient remains well with no further worsening in his disease. Key learning points Sarcoidosis is a clinical entity with no one specific test. The diagnosis should be constructed using multiple parameters including radiographic findings, biochemical and histological proof. We advocate that suspected cases of sarcoidosis should have a thorough assessment and discussion in the MDT. When isolated skin disease is suspected or confirmed, baseline testing for extra-cutaneous involvement should be sent including NT-proBNP, troponin I and T, creatinine kinase, a full pituitary profile, ACE and cytokine assessment for Il2Ra, amongst other routine blood tests. An ECG is of paramount importance as arrhythmias are common cardiac features of sarcoidosis. Should there be ongoing suspicion of multiple organ involvement, a CT-PET should be performed at baseline. Isolated lymph node disease does not commonly warrant treatment; however, this cohort of patients should be closely monitored. The management of sarcoidosis in the acute setting is commonly prednisolone, but steroid sparing therapies should be considered in patients needing recurrent, prolonged courses of corticosteroids or those with evidence of critical organ involvement such as CNS, cardiac or lung disease. Life threatening disease or disease refractory to DMARD therapy should be considered for anti-TNF therapy with infliximab or adalimumab. More recently, tofacitinib has been promising as a treatment for sarcoidosis with clinical trials in Yale and Portland. Newer therapies in development include the GM-CSF inhibitor namilumab, and efzofitimod, a neuropilin 2 inhibitor.
Topical negative pressure is an effective technique to promote wound healing and the integration of skin graft and synthetic dermal equivalents. We describe an in vitro model to investigate the effect of negative pressure on angiogenesis, a pivotal step. Dermal fibroblasts or human microvascular endothelial cells were cultured on Integra and subjected to intermittent or continuous negative pressure. At fixed intervals of over 120 hours, the Integra was fixed and assessed for cell migration (microscopy), cell viability (MTS assay), and cell proliferation (Ki67 immunostaining). Under control conditions, endothelial cells formed a monolayer and failed to ingress, whereas fibroblasts migrated throughout the Integra within 24 hours. Negative pressure switches endothelial cell to a migratory and proliferative phenotype. Ingress is greatest with intermittent rather than continuous negative pressure. It has no effect on dermal fibroblast function. This study identifies an important, potential pro-angiogenic mechanism by which topical negative pressure promotes wound healing.
Pigeon intestinal mucin has been implicated as an important antigen pigeon fanciers' lung. This study investigated whether mucin is detectable in pigeon droppings and bloom, the likely antigenic sources in disease.Soluble extracts of a number of materials found in a pigeon loft were prepared and specific IgG subclass antibodies to these antigens were measured in 14 antibody-positive pigeon fanciers. Cross-reactivity between these materials and purified pigeon intestinal mucin was investigated by inhibition of anti-mucin ELISA. Mucin was purified from the soluble extracts of these crude antigen mixtures by CsCl density gradient centrifugation.The patterns of IgG subclass responses to purified pigeon intestinal mucin and to the four materials collected from the pigeon loft were similar. Subclass differences between symptomatic and asymptomatic individuals, demonstrable against purified mucin, were similarly seen against pigeon droppings and pigeon bloom. Both pigeon droppings and pigeon bloom were capable of inhibiting IgG binding to purified pigeon mucin, and mucin inhibited substantially the binding of IgG to these materials. Glycoprotein with a density similar to that described for pigeon intestinal mucin was purified from each source.Pigeon intestinal mucin is present in a variety of materials found in the environment of the pigeon loft in a form capable of reacting with anti-mucin antibodies in the sera of exposed individuals. Reduction in exposure to these materials may decrease the likelihood of developing pigeon fanciers' lung and minimise reactions in sensitised individuals.
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