Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Chanouzas, Dimitrios; Sagmeister, Michael; Faustini, Sian; Richter, Alex; Ferro, Charles J.; Morgan, Matthew D.; Moss, Paul; Harper, Lorraine

doi:10.1093/infdis/jiy493

Cited by 33 publications

(40 citation statements)

References 31 publications

(29 reference statements)

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“…For the CD4 + T cells, we noted increased expression of CD25 and an increased frequency of cells expressing the NK cell marker CD56. CD4 + T cells expressing CD56 are increased in frequency in patients infected with CMV and noted to be highly cytolytic (32,33). Expansion of CD56 + CD4 + T cells may be indicative of reactivation of latent CMV associated with diminished IgM following splenectomy (32,34,35).…”

Section: Discussionmentioning

confidence: 99%

“…These vaccines may play a role in the global immune perturbations we observed following splenectomy. Furthermore, these vaccines have been shown to increase the expression of CCR4 and CCR6 (32). However, these vaccines are generally given at least 2 wk prior to surgery (44), and with the presplenectomy blood draws occurring on the day of surgery, it is unlikely that the presplenectomy and postsplenectomy blood draws would differ drastically because of responses to these vaccines.…”

Section: Discussionmentioning

confidence: 99%

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High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes

et al. 2020

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Although the consequences of splenectomy are well understood in mice, much less is known about the immunologic changes that occur following splenectomy in humans. We sought to characterize the circulating immune cell populations of patients before and after elective splenectomy to determine if these changes are related to postsplenectomy survival outcomes. Retrospective clinical information was collected from 95 patients undergoing elective splenectomy compared with 91 patients undergoing pancreaticoduodenectomy (Whipple procedure). We further analyzed peripheral blood from five patients in the splenectomy group, collected before and after surgery, using single-cell cytometry by time-of-flight mass spectrometry. We compared pre-and postsplenectomy data to characterize both the major and minor immune cell populations in significantly greater detail. Compared with patients undergoing a Whipple procedure, splenectomized patients had significant and long-lasting elevated counts of lymphocytes, monocytes, and basophils. Cytometry by time-of-flight mass spectroscopy analysis demonstrated that the elevated lymphocytes primarily consisted of naive CD4 + T cells and a population of activated CD25 + CD56 + CD4 + T cells, whereas the elevated monocyte counts were mainly mature, activated monocytes. We also observed a significant increase in the expression of the chemokine receptors CCR6 and CCR4 on several cellular populations. Taken together, these data indicate that significant immunological changes take place following splenectomy. Whereas other groups have compared splenectomized patients to healthy controls, this study compared patients undergoing elective splenectomy to those undergoing a similar major abdominal surgery. Overall, we found that splenectomy results in significant long-lasting changes in circulating immune cell populations and function. ImmunoHorizons, 2020, 4: 82-92.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes

et al. 2020

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“…CD4 + CD28cytotoxic T cells found in the blood of patients with GPA are linked to cytomegalovirus (CMV) infection, which is itself associated with poor AAV outcomes 133 . Furthermore, subclinical CMV infection and reactivation in immunosuppressed patients with AAV may impair immune responses to infection, as the antiviral drug valacyclovir improved vaccine responses in CMV-seropositive patients with AAV 134 .…”

Section: T Cells and Cellular Immunitymentioning

confidence: 99%

ANCA-associated vasculitis

Kitching

Anders

Basu

et al. 2020

Nat Rev Dis Primers

596

507

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The anti-neutrophil cytoplasmic antibody (ANCA)associated vasculitides (AAVs) are diseases characterized by inflammation of blood vessels, endothelial injury and tissue damage. The three types of small-vessel vasculitis, namely granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic GPA (EGPA; previously known as Churg-Strauss syndrome), feature a loss of tolerance to neutrophil primary granule proteins, most often leukocyte proteinase 3 (PR3; also known as myeloblastin) or myeloperoxidase (MPO) (Table 1). The vessels involved in AAV are typically capillaries, arterioles and venules but small arteries and veins may also be affected. Autoimmunity is documented clinically by serum ANCAs to PR3 (PR3-ANCA) or MPO (MPO-ANCA), which are generally associated with the main syndromic AAV presentations (box 1). AAVs collectively represent one of several types of autoimmune vasculitis (Fig. 1). GPA and MPA can involve small blood vessels in any organ or tissue but commonly affect the upper and lower respiratory tract and the kidneys (box 2). Patients with AAV typically present with severe organ-threatening or life-threatening disease, although less severe presentations also occur. GPA is predominantly associated with PR3-ANCA and its clinical features typically include sinonasal disease, lower respiratory tract involvement with pulmonary haemorrhage and granulomatous inflammation, and glomerulonephritis. MPA is usually associated with MPO-ANCA and clinical features include more severe renal disease and some of the manifestations of GPA but without granulomatous inflammation. EGPA is characterized by asthma, eosinophilia and, in many (but not all) cases, vasculitis. EGPA is less common than GPA or MPA and, in some cases, is associated with ANCAs, mainly MPO-ANCA (Table 1). Although categorized as a form of AAV, EGPA has less overlap with the other AAVs than that between GPA and MPA with regard to its genetic, pathogenetic, and clinical features and its management and is typically considered a separate entity. Improvements in treatment and prognosis for patients with AAV have resulted from the translation of both preclinical and clinical research findings. Here, we provide an updated overview of the clinical and

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“…The CMV-specific CD4 + CD28-T cells were found to be expanded in CMV+ but not in CMV-RA patients [40]. Treatment with ganciclovir in CMV+ RA patients with vasculitis reduced the number of CD4 + CD28-T cellssuggesting that these cells are driven by CMV infection [41]. Methotrexate treatment of RA has also been shown to reduce the levels of CD4 + CD28-T cells [42].…”

Section: Premature Immunosenescence In Ramentioning

confidence: 99%

Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression

Bauer

2020

Immun Ageing

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Patients with rheumatoid arthritis (RA) develop features of accelerated ageing, including immunosenescence. These changes include decreased thymic functionality, expansion of late-differentiated effector T cells, increased telomeric attrition, and excessive production of cytokines (senescence-associated secretory phenotype). The progression of RA has been associated with the early development of age-related co-morbidities, including osteoporosis, cardiovascular complications, and cognitive impairment. Here I review data supporting the hypothesis that immune-senescence contributes to the aggravation of both articular and extra-articular manifestations. Of note, poor cognitive functions in RA were associated with senescent CD28-T cells, inflammaging, and autoantibodies against brain antigens. The pathways of immune-to-brain communication are discussed and provide the rationale for the cognitive impairment reported in RA.

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Subclinical Reactivation of Cytomegalovirus Drives CD4+CD28null T-Cell Expansion and Impaired Immune Response to Pneumococcal Vaccination in Antineutrophil Cytoplasmic Antibody–Associated Vasculitis

Abstract: NCT01633476.

Cited by 33 publications

References 31 publications

High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes

High-Dimensional Analysis of Postsplenectomy Peripheral Immune Cell Changes

ANCA-associated vasculitis

Accelerated immunosenescence in rheumatoid arthritis: impact on clinical progression

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