Systematic screening for primary immunodeficiencies in patients hospitalized for severe infection in pediatric intensive care unit.

Over 500 primary immunodeficiency diseases (PID) have been described, but immunological assessment after a severe infection is not routine. We aimed to evaluate the feasibility of a PID screening protocol and calculate PID prevalence in children admitted for severe infection in a pediatric intensive care unit (PICU). This monocentric retrospective study evaluated the feasibility of a PID monitoring protocol after severe infection in children aged 1 month to 16 years-old hospitalized in the Montpellier University Hospital from January 2018 to December 2020.

C3 Glomerulonephritis Associated With Unusual IgG4 Antifactor H in IgG4-related Disease.

C3 glomerulonephritis (C3GN) is characterized by glomerular aggression mediated by deregulation of the alternative complement pathway. C3GN can be inherited or consequent to acquired autoantibodies, notably against factor H. We report the case of a patient with systemic active IgG4-related disease who presented for acute kidney injury with glomerular proteinuria and hypocomplementemia related to C3GN associated with IgG4-related interstitial nephritis on kidney biopsy.

Two New Kindreds with Complete Factor D Deficiency.

Inborn deficiencies of the alternative pathway (AP) of the complement system have been associated with life-threatening infections, mainly by encapsulated bacteria. Complete factor D (FD) deficiencies have been reported in only seven families in the literature. We report two new cases of biochemically and genetically confirmed complete FD deficiency, including the first in a Down syndrome patient.

CD57 EMRA CD8 T cells in cancer patients over 70: associations with prior chemotherapy and response to anti-PD-1/PD-L1 therapy.

Background: Immune ageing complicates cancer treatment in older individuals. While immunotherapy targeting the PD-1/PD-L1 pathway can reinvigorate T cells, these cells tend to become senescent with age. This study investigates different CD8 T cell subsets usually associated with senescence, in cancer patients over 70 years old who are undergoing anti-PD-1/PD-L1 immunotherapy, and examines the relationship between these senescent cells and prior chemotherapy exposure.

C3 glomerulopathy is highly prevalent in French Polynesia.

Objective: To compare the natural history of C3 glomerulopathy (C3G) to acute post-infectious glomerulonephritis (APIGN) in a cohort of patients with a relative homogeneity of environment conditions and genetic background.

Methods: We retrospectively reviewed the characteristics of all patients with biopsy proven C3G or APIGN referred in 2013-2019 to the only renal unit in French Polynesia.

Results: Point prevalence of C3G is ∼23 cases per 100,000 inhabitants.

Acquired and genetic drivers of C3 and C5 convertase dysregulation in C3 glomerulopathy and immunoglobulin-associated MPGN.

Dysregulation of the alternative pathway of complement plays a central role in the pathophysiology of C3 glomerulopathy (C3G). Various autoimmune and genetic factors targeting the alternative pathway have been associated with both C3G and primary immunoglobulin-associated membranoproliferative glomerulonephritis (Ig-MPGN), suggesting shared pathophysiological mechanisms. This review highlights the wide range of disease drivers identified that mainly target components or protein complexes of the alternative pathway, both in C3G and Ig-MPGN.

Acquired and genetic determinants of disease phenotype and therapeutic strategies in C3 glomerulopathy and immunoglobulin-associated MPGN.

C3 glomerulopathy (C3G), a prototype of complement-mediated disease, is characterized by significant heterogeneity, in terms of not only clinical, histological and biological presentation but also prognosis, and response to existing therapies. Recent advancements in understanding the factors responsible for alternative pathway dysregulation in the disease have highlighted its even more complex nature. Here, we propose a reexamination of the diversity of C3G presentations in light of the drivers of complement activation.

Thrombotic Microangiopathy as an Emerging Complication of Viral Vector-Based Gene Therapy.

Gene therapy has brought tremendous hope for patients with severe life-threatening monogenic diseases. Although studies have shown the efficacy of gene therapy, serious adverse events have also emerged, including thrombotic microangiopathy (TMA) following viral vector-based gene therapy. In this review, we briefly summarize the concept of gene therapy, and the immune response triggered by viral vectors.

Hot Spot of Complement Factor I Rare Variant p.Ile357Met in Patients With Hemolytic Uremic Syndrome.

Atypical hemolytic uremic syndrome (aHUS) is a rare kidney disease due to a dysregulation of the complement alternative pathway. Complement factor I (CFI) negatively regulates the alternative pathway and CFI gene rare variants have been associated to aHUS with a low disease penetrance. We report 10 unrelated cases of HUS associated to a rare CFI variant, p.

Multi-Institutional Evaluation of Pathologists' Assessment Compared to Immunoscore.

Background: The Immunoscore (IS) is a quantitative digital pathology assay that evaluates the immune response in cancer patients. This study reports on the reproducibility of pathologists' visual assessment of CD3+- and CD8+-stained colon tumors, compared to IS quantification.

Methods: An international group of expert pathologists evaluated 540 images from 270 randomly selected colon cancer (CC) cases.

Rare Variants in Complement Gene in C3 Glomerulopathy and Immunoglobulin-Mediated Membranoproliferative GN.

Background: C3 glomerulopathy and idiopathic immunoglobulin-mediated membranoproliferative GN (Ig-MPGN) are rare complement-mediated kidney diseases. Inherited forms of C3 glomerulopathy/Ig-MPGN are rarely described.

Methods: Three hundred ninety-eight patients with C3 glomerulopathy ( n =296) or Ig-MPGN ( n =102) from a national registry were screened for three complement genes: factor H ( CFH ), factor I ( CFI ), and C3 .

Disseminated Cryptococcosis Following Eculizumab Therapy: Insight Into Pathogenesis.

Eculizumab, a recombinant humanized monoclonal antibody (mAb), is used for the treatment of patients (both adults and children) with paroxysmal nocturnal hemoglobinuria and atypical hemolytic uremic syndrome. This mAb binds to complement protein 5 (C5), thereby inhibiting its cleavage. On the other hand, one of the C5 cleavage products, C5a, is a potent anaphylatoxin with proinflammatory properties, involved in antimicrobial surveillance.

C3 Glomerulopathy With Concurrent Thrombotic Microangiopathy: Clinical and Immunological Features.

Rationale & Objective: C3 glomerulopathy (C3GN) and atypical hemolytic uremic syndrome (aHUS) are 2 distinct rare kidney diseases caused by dysregulation of the alternative complement pathway. Patients with C3GN and concurrent kidney lesions of thrombotic microangiopathy (TMA) have been rarely reported. We characterized the clinical features and underlying immunological abnormalities in these patients.

Clinical Performance of the Consensus Immunoscore in Colon Cancer in the Asian Population from the Multicenter International SITC Study.

BACKGROUND: In this study, we evaluated the prognostic value of Immunoscore in patients with stage I−III colon cancer (CC) in the Asian population. These patients were originally included in an international study led by the Society for Immunotherapy of Cancer (SITC) on 2681 patients with AJCC/UICC-TNM stages I−III CC. METHODS: CD3+ and cytotoxic CD8+ T-lymphocyte densities were quantified in the tumor and invasive margin by digital pathology.

The "Immunoscore" in rectal cancer: could we search quality beyond quantity of life?

Because of the function and anatomical environment of the rectum, therapeutic strategies for local advanced rectal cancer (LARC) must deal with two challenging stressors that are a high-risk of local and distal recurrences and a high-risk of poor quality of life (QoL). Over the last three decades, advances in screening tests, therapies, and combined-modality treatment options and strategies have improved the prognosis of patients with LARC. However, owing to the heterogeneous nature of LARC and genetic status, the patient may not respond to a specific therapy and may be at increased risk of side-effects without the life-prolonging benefit.