Peripheral B Cell Deficiency and Predisposition to Viral Infections: The Paradigm of Immune Deficiencies.

In the era of COVID-19, understanding how our immune system responds to viral infections is more pertinent than ever. Immunodeficiencies with very low or absent B cells offer a valuable model to study the role of humoral immunity against these types of infection. This review looks at the available evidence on viral infections in patients with B cell alymphocytosis, in particular those with X-linked agammaglobulinemia (XLA), Good's syndrome, post monoclonal-antibody therapy and certain patients with Common Variable Immune Deficiency (CVID). Viral infections are not as infrequent as previously thought in these conditions and individuals with very low circulating B cells seem to be predisposed to an adverse outcome. Particularly in the case of SARS-CoV2 infection, mounting evidence suggests that peripheral B cell alymphocytosis is linked to a poor prognosis.

CNS demyelination associated with immune dysregulation and a novel CTLA-4 variant.

BACKGROUND: The cytotoxic T-lymphocyte antigen-4 (CTLA-4) pathway acts as a negative immune regulator of T-cell activation and promotes self-tolerance. CASE: We report the first case of biopsy-proven central nervous system inflammatory demyelination in the context of primary immunodeficiency and a novel CTLA-4 variant. CONCLUSION: This case has significant implications for the development of novel treatments for autoimmune conditions including multiple sclerosis and further emphasises the need for caution with clinical use of CTLA-4 immune checkpoint inhibitors in those with a history of inflammatory demyelination.

Clinically significant depressive symptoms and sexual behaviour among men who have sex with men.

BACKGROUND: The relationship between depression and sexual behaviour among men who have sex with men (MSM) is poorly understood. AIMS: To investigate prevalence and correlates of depressive symptoms (Patient Health Questionnaire-9 score ≥10) and the relationship between depressive symptoms and sexual behaviour among MSM reporting recent sex. METHOD: The Attitudes to and Understanding of Risk of Acquisition of HIV (AURAH) is a cross-sectional study of UK genitourinary medicine clinic attendees without diagnosed HIV (2013-2014). RESULTS: Among 1340 MSM, depressive symptoms (12.4%) were strongly associated with socioeconomic disadvantage and lower supportive network. Adjusted for key sociodemographic factors, depressive symptoms were associated with measures of condomless sex partners in the past 3 months (≥2 (prevalence ratio (PR) 1.42, 95% CI 1.17-1.74; P=0.001), unknown or HIV-positive status (PR 1.43, 95% CI 1.20-1.71; P<0.001)), sexually transmitted infection (STI) diagnosis (PR 1.46, 95% CI 1.19-1.79; P<0.001) and post-exposure prophylaxis use in the past year (PR 1.83, 95% CI 1.33-2.50; P<0.001). CONCLUSIONS: Management of mental health may play a role in HIV and STI prevention. DECLARATION OF INTEREST: A.N.P. has received payments for presentations made at meetings sponsored by Gilead in spring 2015. N.C.N. has received support for attendance at conferences, speaker fees and payments for attendance at advisory boards from Gilead Sciences, Viiv Healthcare, Janssen Pharmaceuticals and Bristol-Myers Squibb and a research grant from Gilead Sciences. D.A. served on the advisory board for Gilead in January 2016. M.M.G. has had sponsorship to attend conferences by Bristol-Myers Squibb, been on the BioCryst advisory board and run trials for Merck, Gilead, SSAT, BioCryst and Novartis. COPYRIGHT AND USAGE: © The Royal College of Psychiatrists 2017. This is an open access article distributed under the terms of the Creative Commons Non-Commercial, No Derivatives (CC BY-NC-ND) license.

British Lung Foundation/United Kingdom Primary Immunodeficiency Network Consensus Statement on the Definition, Diagnosis, and Management of Granulomatous-Lymphocytic Interstitial Lung Disease in Common Variable Immunodeficiency Disorders.

A proportion of people living with common variable immunodeficiency disorders develop granulomatous-lymphocytic interstitial lung disease (GLILD). We aimed to develop a consensus statement on the definition, diagnosis, and management of GLILD. All UK specialist centers were contacted and relevant physicians were invited to take part in a 3-round online Delphi process. Responses were graded as Strongly Agree, Tend to Agree, Neither Agree nor Disagree, Tend to Disagree, and Strongly Disagree, scored +1, +0.5, 0, -0.5, and -1, respectively. Agreement was defined as greater than or equal to 80% consensus. Scores are reported as mean ± SD. There was 100% agreement (score, 0.92 ± 0.19) for the following definition: "GLILD is a distinct clinico-radio-pathological ILD occurring in patients with [common variable immunodeficiency disorders], associated with a lymphocytic infiltrate and/or granuloma in the lung, and in whom other conditions have been considered and where possible excluded." There was consensus that the workup of suspected GLILD requires chest computed tomography (CT) (0.98 ± 0.01), lung function tests (eg, gas transfer, 0.94 ± 0.17), bronchoscopy to exclude infection (0.63 ± 0.50), and lung biopsy (0.58 ± 0.40). There was no consensus on whether expectant management following optimization of immunoglobulin therapy was acceptable: 67% agreed, 25% disagreed, score 0.38 ± 0.59; 90% agreed that when treatment was required, first-line treatment should be with corticosteroids alone (score, 0.55 ± 0.51).

False interpretation of diagnostic serology tests for patients treated with pooled human immunoglobulin G infusions: a trap for the unwary.

Therapeutic immunoglobulin G (IgG) products are produced from numerous plasma donations, and are infused in many medical conditions. The serological testing of patients who have received IgG infusions may well produce falsely positive and misleading results from this infused IgG, rather than endogenously produced IgG. We present two example cases of clinical situations where this could cause concern. We tested multiple IgG products with a range of serological tests performed in infective or autoimmune conditions, including hepatitis B, syphilis, human immunodeficiency virus, human T-lymphotropic virus, anti-neutrophil cytoplasmic antibody (ANCA), anti-nuclear antibody (ANA), anti-cardiolipin antibodies and anti-double stranded DNA (dsDNA) antibody. We found positivity within these products for hepatitis B surface and core antibody, syphilis, ANCA, ANA, anti-cardiolipin IgG and dsDNA antibody, which may result from specific or non-specific reactivity. The serological testing of patients who have received IgG treatment detects the administered IgG in addition to IgG produced by the patient.

Correct recognition and management of anaphylaxis: not much change over a decade.

BACKGROUND: Anaphylaxis is increasing in incidence. This potentially fatal condition requires immediate intramuscular adrenaline as a vital part of early treatment. A 2002 survey of UK Senior House Officers showed a lack of knowledge regarding the recognition and management of anaphylaxis. Since then major changes in medical education and updated national guidelines have aimed to ensure that doctors can recognise and treat anaphylaxis appropriately. OBJECTIVES: To determine current knowledge concerning the recognition and management of anaphylaxis among junior doctors compared to their predecessors. METHODS: Using the same methodology as in 2002, we asked 68 Foundation doctors to read five clinical scenarios potentially suggesting anaphylaxis and indicate how they would respond to each case. Their results were compared to those of Senior House Officers in 2002. RESULTS: 68 of 107 (64%) junior doctors completed the questionnaire. All recognised the need for adrenaline in anaphylaxis, but only 74% selected the correct intramuscular route, and 34% the correct route and dose. 82% of junior doctors would inappropriately give adrenaline to the patient who had inhaled a foreign body (case 2). A higher percentage of the 2013 cohort indicated the correct route and dose of adrenaline in anaphylaxis than their 2002 colleagues. However, a greater percentage also selected adrenaline treatment inappropriately in non-anaphylactic case scenarios. CONCLUSIONS: Despite updated guidelines, junior doctors continue to have poor knowledge about the recognition and management of anaphylaxis, with some still considering inappropriate intravenous adrenaline. More effort should be given to the recognition of anaphylaxis in early medical training.

Cinryze (C1-inhibitor) for the treatment of hereditary angioedema.

Cinryze is a pasteurized, nanofiltered plasma derived concentrate of C1-inhibitor (pdC1-INH) licensed for the prophylactic treatment of hereditary angioedema. In a double-blind placebo-controlled crossover trial to evaluate Cinryze as prophylaxis, the frequency of attacks was halved (6.26 per 12 weeks on Cinryze versus 12.73 per 12 weeks on placebo). Furthermore, attacks were generally milder and of shorter duration. For treatment of acute attacks in patients receiving Cinryze, 1000 units, within 4 h of the start of an attack, the estimated time to the onset of unequivocal relief was reduced to 2 h, compared with more than 4 h in those treated with placebo. Cinryze and other similar products are going to change the future management of hereditary angioedema and have potential in other areas of medicine.

Th1 and Th2 subsets in orthopaedic surgery by single-cell cytokine analysis.

Significant immunosuppression can occur following allogeneic blood transfusion or surgery. Cytokine stimulation controls immune responses and determines their type and intensity. Infusion of autologous or allogeneic blood provides elements, including cytokines, which may result in transfusion-associated immunomodulation. This study investigates to what extent autologous/cell salvage transfusions affect levels of intracellular cytokines interferon-gamma and interleukin-4, and if this indicates a shift in the T-helper 1/T-helper 2 cell ratio using a novel method of detecting intracellular cytokines, the Magnetic Activated Cell Sorter Cytokine Secretion Assay (MACS Assay). Comparisons were made between patients receiving autologous blood or no blood transfusion, for pre- and post-operation levels of interferon-gamma and interleukin-4. Interferon-gamma producing T-helper 1 cells decreased post-operatively. Concomitantly, interleukin-4 producing T-helper 2 cells increase. These results demonstrate a measurable shift from T-helper 1 to T-helper 2 cells post-operatively. Secondly, the study showed surgery alone instigates the same level of immunomodulation as autologous/cell salvage blood transfusion in combination with surgery.