Human papillomavirus (HPV)-induced cutaneous warts are potentially serious and debilitating. In immunosuppressed patients, these warts may be resistant to standard therapies. We report a case of a young patient with a primary immune deficiency whose recalcitrant cutaneous warts regressed completely following administration of a quadrivalent HPV vaccine.
The involvement of IgG3 within the humoral immune response to SARS-CoV2 infection has been implicated in the pathogenesis of ARDS in COVID-19. The exact molecular mechanism is unknown but is thought to involve this IgG subtypes differential ability to fix complement and stimulate cytokine release. We examined convalescent patients antibodies binding to immobilised nucleocapsid and spike protein by MALDI-ToF mass spectrometry. IgG3 was a major immunoglobulin found in all samples. Differential analysis of the spectral signatures found for nucleocapsid versus spike protein demonstrated that the predominant humoral immune response to nucleocapsid was IgG3, whilst against spike it was IgG1. However, the spike protein displayed a strong affinity for IgG3 itself which it would bind from control plasma samples as well as from those previously infected with SARS-CoV2, much in the way Protein-G binds IgG1. Furthermore, detailed spectral analysis indicated a mass shift consistent with hyper-glycosylation or glycation was a characteristic of the IgG3 captured by the spike protein.
The prefusion Spike protein of SARS-CoV2 binds advanced glycation end product (AGE) glycated human serum albumin (HSA) and a higher mass, hyperglycosylated/glycated, IgG3, as determined by matrix assisted laser desorption mass spectrometry (MALDI-ToF MS). We set out to investigate if the total blood plasma of patients who had recovered from acute respiratory distress as a result of COVID-19, contained more glycated HSA and higher mass (glycosylated/glycated) IgG3 than those with only clinically mild or asymptomatic infections. A direct dilution and disulphide bond reduction method was development and applied to plasma samples from SARS-CoV2 seronegative (N = 30) and seropositive (N = 31) healthcare workers and 38 convalescent plasma samples from patients who had been admitted with acute respiratory distress syndrome (ARDS) associated with COVID-19.Patients recovering from COVID-19 ARDS had significantly higher mass, AGE-glycated HSA and higher mass IgG3 levels. This would indicate that increased levels and/or ratios of hyper-glycosylation (probably terminal sialic acid) IgG3 and AGE glycated HSA may be predisposition markers for development of ARDS as a result of COVID-19 infection. Furthermore, rapid direct analysis of plasma samples by MALDI-ToF MS for such humoral immune correlates of COVID-19 presents a feasible screening technology for the most at risk; regardless of age or known health conditions.Abstract Figure
IntroductionThere is increasing evidence of an association between Idiopathic Pulmonary Arterial Hypertension (IPAH) and immune dysregulation. Amongst other evidence, autoantibodies are detected in IPAH and there is a high prevalence of autoimmune conditions associated with group 1 pulmonary arterial hypertension.1 Previous work has focussed on a role for T-regulatory cells in IPAH, however, we have noted a more profound general lymphopaenia clinically, which we set out to define and investigate.ObjectivesTo phenotype circulating leucocytes in patients with IPAH.MethodsFresh peripheral blood leucocytes from patients with IPAH were compared to age and sex-matched healthy controls. A standardised flow cytometry panel for cell surface markers of leucocyte sub-populations was adapted from the Human Immunology Project.2 Additionally Ig subclasses in serum were analysed by PEG enhanced immunoturbidometric assay and nephelometry. Peripheral lung tissue from explants in patients with IPAH was compared to control tissue from lung tumour resection (distant to the tumour margin). Tissue was immunostained for complement fragments C3d and C4d by streptABC peroxidase technique and visualised with 3,39-DAB hydrochloride and imaged by light microscopy.ResultsOverall lymphocyte counts were significantly reduced in IPAH compared to controls (p = 0.0187). Despite this, IPAH patients demonstrated significantly increased populations of T follicular helper (Tfh) cells (p = 0.0007) and PD1+CD4+ T-cells (p = 0.0028), associated with T-cell exhaustion and control of Tfh mediated humoral immunity. There was evidence of altered B-cell differentiation with increased transitional cells (p = 0.01) and decreased non-switched memory cells (p = 0.001). Ig subclasses were not statistically different between IPAH and control and complement deposition was not significantly different between disease and control in precapillary lung vessels.ConclusionsThere is evidence of immune dysfunction in IPAH, notably consistent with previous reports in autoimmunity. Dysregulated immunity is emerging as a potentially important factor in IPAH pathogenesis.Abstract S5 Figure 1IPAH patients demonstrated significantly increased populations of T follicular helper (Tfh) cells and PD1+CD4+ T-cells compared to healthy controlsReferences1 Mouthon L, Guillevin L, Humbert M. Pulmonary arterial hypertension: an autoimmune disease? Eur. Respir. J. 2005;26(6):986–82 Maecker HT, McCoy JP, Nussenblatt R. Standardizing immunophenotyping for the Human Immunology Project. Nat. Rev. Immunol. 2012;12(3):191–200
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