Monogenic lupus: Dissecting heterogeneity

Omarjee, Ommar; Picard, Cécile; Frachette, Cécile; Moreews, Marion; Rieux-Laucat, Frédéric; Soulas-Sprauel, Pauline; Viel, Sébastien; Lega, Jean‐Christophe; Bader‐Meunier, Brigitte; Walzer, Thierry; Mathieu, Anne-Laure; Cimaz, Rolando; Belot, Alexandre

doi:10.1016/j.autrev.2019.102361

Cited by 102 publications

(71 citation statements)

References 89 publications

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“…Early onset disease in prepubertal period, evidence of mendelian inheritance or strong family history, less typical manifestations such as severe skin, neurologic or joint disease and refractoriness to standard therapy should raise the suspicion for monogenic lupus. Majority are caused by defect in genes of complement system and Type-1 interferon regulation [1]. Type-1 interferonopathies include Aicardi-Goutières syndrome (AGS) and SPENCDI [2].…”

Section: Discussionmentioning

confidence: 99%

“…Monogenic lupus accounts for a small subset of systemic lupus erythematosus (SLE) and commonly caused by Type-1 interferonopathies and defects in complement system [1]. Spondyloenchondrodysplasia with immune dysregulation (SPENCDI) is a Type-1 interferonopathy and a rare autosomal recessive skeletal dysplasia characterized by radiolucent vertebral and metaphyseal lesions.…”

Section: Introductionmentioning

confidence: 99%

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Monogenic Lupus with IgA Nephropathy Caused by Spondyloenchondrodysplasia with Immune Dysregulation

et al. 2021

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Monogenic disorders causing systemic lupus erythematosus represent a small subset of cases. Type-1 interferonopathies, like spondyloenchondrodysplasia with immune dysregulation constitute an important functional category of monogenic lupus. Apart from autoimmune disorders, neurological and skeletal abnormalities are additional manifestations observed in this disorder. A young female presented with seizures due to acute hemorrhagic stroke secondary to malignant hypertension. On evaluating the cause for hypertension, there was evidence of glomerulonephritis and multiple autoantibodies positivity including dsDNA. A diagnosis of lupus was made based on clinical and laboratory findings. Kidney biopsy revealed mesangial proliferative glomerulonephritis with predominant IgA deposits favouring IgA nephropathy. Additional features in the form of short stature with vertebral abnormalities and bilateral basal ganglia calcification led to evaluation of Type-1 interferonopathies. Sanger sequencing identified a novel compound heterozygous variants c.550C>T (p.Q184*) in exon 3 and c.740T>G (p.L247R) in exon 4 of ACP5 gene. Parents were found to be carriers of the variants in ACP5 gene. Management included antihypertensive agents and symptomatic therapy. On follow-up, there was complete resolution of glomerulonephritis and normalization of blood pressure. This case report documents the classic phenotype comprising autoimmune, skeletal, and neurological abnormalities in spondyloenchondrodysplasia with immune dysregulation with a novel variant on Sanger sequencing in an Indian patient. This report also highlights the rare coexistence of IgA nephropathy in monogenic lupus.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Monogenic Lupus with IgA Nephropathy Caused by Spondyloenchondrodysplasia with Immune Dysregulation

et al. 2021

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“…Experimental evidence showed that the main pathogenic events in SLE could be found in a primary dysregulation of innate immunity, which triggers, sustains, and drives the consequent adaptive immune response with the production of a plethora of autoantibodies (and autoreactive B- and T-cells), leading to the complete and very heterogeneous clinical expression of SLE [ 38 ]. Therefore, it is reasonable to consider that basophils may promote or affect this pathologic process as well, if they can influence B-cell polarization and the production of specific types of autoantibodies.…”

Section: Discussionmentioning

confidence: 99%

“…Very briefly and schematically, three main pathogenic mechanisms have been recognized in SLE so far, which may be variably represented in different patients: (i) self-antigen excess (or reduced clearance; known as an “efferocytosis defect” that may be promoted by some constitutive complement defects associated with SLE, especially in pediatric cases), (ii) apoptosis defect, primarily affecting B-cell proliferation and tolerance, (iii) inappropriate activation of type I interferon responses (“type I interferonopathy”), which may cause a primary and inappropriate chronic inflammatory response, sustaining the autoimmune process [ 38 , 39 , 40 ].…”

Section: Introductionmentioning

confidence: 99%

Basophils and Systemic Lupus Erythematosus in Murine Models and Human Patients

Dossybayeva

Abdukhakimova

Poddighe

2020

Biology

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Basophils are the rarest cell population in the blood. Even though basophils are known to participate in some allergic reactions and immune responses to parasitic infections, their immunological role is still largely elusive. Recent evidence has suggested that in some murine models of systemic lupus erythematosus and lupus-like nephritis, basophils may also be implicated in autoimmunity processes by promoting autoantibody production and tissue injury. We conducted a systematic search to collect the available evidence on basophils’ potential immunomodulatory role in autoimmunity and, particularly, systemic lupus erythematosus. We identified several articles investigating basophils’ role in murine models of lupus (n = 3) and in patients affected with systemic lupus erythematosus (n = 8). Even though the alteration of the “adaptive” immune response is considered the main immunopathological event in systemic lupus erythematosus, the contribution from the mechanisms of “innate” immunity and, particularly, basophils may be relevant as well, by modulating the activation, polarization, and survival of lymphocytes.

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“…The link between complement protein deficiency and IFN type I upregulation is currently under investigation. A defect of the opsonization of apoptotic self-bodies and, therefore, of the cellular clearance and the "efferocytosis" is considered the main causative factor (69). In addition, it was demonstrated that C1q in vitro inhibits peripheral blood mononuclear cell (PBMCs) and plasmacytoid dendritic cell IFNα production, thus hypothesizing a direct C1q regulatory role (72).…”

Section: Monogenic Systemic Lupus Erythematosusmentioning

confidence: 99%

Type I Interferonopathies in Children: An Overview

et al. 2021

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Notable advances in gene sequencing methods in recent years have permitted enormous progress in the phenotypic and genotypic characterization of autoinflammatory syndromes. Interferonopathies are a recent group of inherited autoinflammatory diseases, characterized by a dysregulation of the interferon pathway, leading to constitutive upregulation of its activation mechanisms or downregulation of negative regulatory systems. They are clinically heterogeneous, but some peculiar clinical features may lead to suspicion: a familial “idiopathic” juvenile arthritis resistant to conventional treatments, an early necrotizing vasculitis, a non-infectious interstitial lung disease, and a panniculitis associated or not with a lipodystrophy may represent the “interferon alarm bells.” The awareness of this group of diseases represents a challenge for pediatricians because, despite being rare, a differential diagnosis with the most common childhood rheumatological and immunological disorders is mandatory. Furthermore, the characterization of interferonopathy molecular pathogenetic mechanisms is allowing important steps forward in other immune dysregulation diseases, such as systemic lupus erythematosus and inflammatory myositis, implementing the opportunity of a more effective target therapy.

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Monogenic lupus: Dissecting heterogeneity

Cited by 102 publications

References 89 publications

Monogenic Lupus with IgA Nephropathy Caused by Spondyloenchondrodysplasia with Immune Dysregulation

Monogenic Lupus with IgA Nephropathy Caused by Spondyloenchondrodysplasia with Immune Dysregulation

Basophils and Systemic Lupus Erythematosus in Murine Models and Human Patients

Type I Interferonopathies in Children: An Overview

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