Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?

Ingegnoli, Francesca; Gualtierotti, Roberta; Schioppo, Tommaso; Orenti, Annalisa; Boracchi, Patrizia; Lubatti, C.; Mastaglio, Claudio; Galbiati, Valentina; Murgo, Antonella; Zeni, S.; Grossi, Claudia; Borghi, Maria Orietta; Rosenberg, William; Castelnovo, Laura; Meroni, Pier Luigi

doi:10.1136/annrheumdis-2013-204009

Cited by 4 publications

(3 citation statements)

References 7 publications

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“…Disease activity was determined with SLE disease activity index (SLE DAI-2K; Gladman et al, 2002); clinical and laboratory data were obtained during the routine follow-up. Patients were characterized for antiphospholipid antibodies (Lupus Anticoagulant, anticardiolipin IgG and IgM, and anti-β2GPI IgG and IgM; Andreoli et al, 2015) as well as ANA, anti-ENA, and anti-dsDNA antibodies (Ingegnoli et al, 2014). All experiments performed on human blood samples from HDs were approved by the ethics committee of Fondazione IRC CS Ca' Granda Ospedale Maggiore Policlinico, and informed consent was obtained from all subjects.…”

Section: Human Samples and Patientsmentioning

confidence: 99%

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P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus

Faliti

Gualtierotti

Rottoli

et al. 2019

Journal of Experimental Medicine

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Altered control of T follicular helper (Tfh) cells can lead to generation of autoantibodies and autoimmune manifestations. Signaling pathways that selectively limit pathogenic responses without affecting the protective function of Tfh cells are unknown. Here we show that the ATP-gated ionotropic P2X7 receptor restricts the expansion of aberrant Tfh cells and the generation of self-reactive antibodies in experimental murine lupus, but its activity is dispensable for the expansion of antigen-specific Tfh cells during vaccination. P2X7 stimulation promotes caspase-mediated pyroptosis of Tfh cells and controls the development of pathogenic ICOS+ IFN-γ–secreting cells. Circulating Tfh cells from patients with systemic lupus erythematosus (SLE) but not primary antiphospholipid syndrome (PAPS), a nonlupus systemic autoimmune disease, were hyporesponsive to P2X7 stimulation and resistant to P2X7-mediated inhibition of cytokine-driven expansion. These data point to the P2X7 receptor as a checkpoint regulator of Tfh cells; thus, restoring P2X7 activity in SLE patients could selectively limit the progressive amplification of pathogenic autoantibodies, which deteriorate patients’ conditions.

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Section: Human Samples and Patientsmentioning

confidence: 99%

“…a Anti-dsDNA has been detected as previously reported (Ingegnoli et al, 2014); anti-dsDNA titers were defined as low if <40 UI/ml, medium/high if >40 UI/ ml.…”

mentioning

confidence: 99%

P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus

Faliti

Gualtierotti

Rottoli

et al. 2019

Journal of Experimental Medicine

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“…A mounting quantity of evidences provides a rationale for the use of RTX in SSc patients 66–68. The most significant studies on RTX in SSc are reported in Table 3.…”

Section: Rtx In Systemic Sclerosis (Ssc)mentioning

confidence: 99%

Current perspective on rituximab in rheumatic diseases

Schioppo¹,

Ingegnoli²

2017

DDDT

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The steadily increasing knowledge regarding pathogenetic mechanisms in autoimmune rheumatic diseases has paved the way to different therapeutic approaches. In particular, the market entry of biologics has dramatically modified the natural history of rheumatic chronic inflammatory diseases with a meaningful impact on patients’ quality of life. Among the wide spectrum of available biological treatments, rituximab (RTX), first used in the treatment of non-Hodgkin’s lymphoma, was later approved for rheumatoid arthritis and anti-neutrophil cytoplasmic antibodies-associated vasculitis. Nowadays, in rheumatology, RTX is also used with off-label indications in patients with systemic sclerosis, Sjögren’s syndrome and systemic lupus erythematosus. RTX is a monoclonal antibody directed to CD20 molecules expressed on the surfaces of pre-B and mature B lymphocytes. It acts by causing apoptosis of these cells with antibody- and complement-dependent cytotoxicity. As inflammatory responses to cell-associated immune complexes are key elements in the pathogenesis of several autoimmune rheumatic diseases, such an approach might be effective in these patients. In fact, RTX, by promoting the rapid and long-term depletion of circulating and lymphoid tissue-associated B cells, leads to a lower recruitment of these effector cells at sites of immune complex deposition, thus reducing inflammation and tissue damage. RTX is of the most interest to rheumatologists as it represents an important additional therapeutic approach. Thus, the advent in clinical practice of approved RTX biosimilars, such as CT-P10, may be of help in improving treatment access as well as in reducing costs.

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Update on Juvenile Systemic Sclerosis

Foeldvari¹

2015

Curr Rheumatol Rep

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Juvenile systemic sclerosis is an orphan disease of the macro- and microvasculature with an unknown etiology. Although pediatric and adult classification systems have been developed, neither has been validated yet. Recent publications have shown a shift in the subset pattern in juvenile-onset adult patients, with a better outcome in these patients as compared with young adult patients. As a first step in assessing activity, damage, and severity, a pediatric severity score--a modification of the adult Medsger scale--was proposed but has not been validated. An activity score also has been developed but has not yet been published. Currently, treatment approaches are based only on adult data, and problems exist in extrapolating these data to a pediatric population.

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Fibrosis biomarkers in isolated Raynaud's phenomenon: too little, too soon?

Cited by 4 publications

References 7 publications

P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus

P2X7 receptor restrains pathogenic Tfh cell generation in systemic lupus erythematosus

Current perspective on rituximab in rheumatic diseases

Update on Juvenile Systemic Sclerosis

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