PapersFlow Research Brief
Immunodeficiency and Autoimmune Disorders
Research Guide
What is Immunodeficiency and Autoimmune Disorders?
Immunodeficiency and autoimmune disorders are conditions characterized by dysfunctions of the immune system, including deficiencies that increase susceptibility to infections and autoimmune responses where the immune system attacks the body's own tissues.
The field encompasses 99,017 published works examining mechanisms linking immune deficiencies to autoimmunity. Research highlights roles of T helper cell subsets like Th17 cells in driving pathogenic inflammation, as detailed in foundational studies on IL-17 and IL-23 pathways. Clinical advancements include therapies like infliximab for maintaining remission in Crohn's disease and ulcerative colitis.
Research Sub-Topics
Primary Immunodeficiency Disorders
This sub-topic studies genetic defects in immune system development and function, including SCID and CVID. Researchers focus on gene identification, pathophysiology, and hematopoietic stem cell transplantation outcomes.
Th17 Cell Differentiation in Autoimmunity
This sub-topic examines cytokine regulation of Th17 differentiation, plasticity, and pathogenic functions in autoimmune diseases. Researchers investigate IL-23/IL-17 axis and therapeutic targeting.
NOD2 Mutations in Crohn's Disease
This sub-topic explores NOD2/CARD15 genetic variants, bacterial sensing defects, and Crohn's disease susceptibility. Researchers study autophagy, Paneth cell function, and genotype-phenotype correlations.
T Regulatory Cell Therapy
This sub-topic investigates Treg expansion, stability, and adoptive transfer for immune tolerance induction. Researchers develop protocols for autoimmunity, transplantation, and GVHD prevention.
Common Variable Immunodeficiency Pathogenesis
This sub-topic covers B cell intrinsic defects, T cell dysregulation, and autoimmunity in CVID. Researchers identify monogenic causes and biomarkers for disease stratification.
Why It Matters
Immunodeficiency and autoimmune disorders impact treatment of inflammatory bowel diseases and primary immunodeficiencies, with specific therapies demonstrating measurable clinical benefits. In the ACCENT I trial, maintenance infliximab therapy resulted in higher rates of clinical remission in Crohn's disease patients compared to placebo (Hanauer et al., 2002, "Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial"). Similarly, infliximab induction and maintenance increased clinical response rates at weeks 8, 30, and 54 in moderate-to-severe ulcerative colitis (Rutgeerts et al., 2005, "Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis"). Recent developments include FDA acceptance of supplemental NDA for leniolisib in children aged 4-11 with activated phosphoinositide 3-kinase delta syndrome (APDS), addressing a rare immunodeficiency, though a Complete Response Letter was later issued for Joenja (leniolisib). Gene therapy for SCID-X1 corrected immunodeficiency in 9 of 10 patients but led to LMO2-associated clonal T cell proliferation in two cases (Hacein-Bey-Abina et al., 2003, "LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1"). These examples underscore targeted interventions improving survival and quality of life in specific disorders.
Reading Guide
Where to Start
"IL-17 and Th17 Cells" by Korn et al. (2009) provides an accessible review of T cell differentiation into IL-17-producing subsets, foundational for understanding autoimmune mechanisms cited across the field.
Key Papers Explained
Bettelli et al. (2006, "Reciprocal developmental pathways for the generation of pathogenic effector TH17 and regulatory T cells") establishes Th17-Treg balance, extended by Korn et al. (2009, "IL-17 and Th17 Cells") reviewing cytokine profiles and Langrish et al. (2005, "IL-23 drives a pathogenic T cell population that induces autoimmune inflammation") showing IL-23's role. Veldhoen et al. (2006, "TGFβ in the Context of an Inflammatory Cytokine Milieu Supports De Novo Differentiation of IL-17-Producing T Cells") details TGFβ-driven differentiation. Clinical translation appears in Hanauer et al. (2002, "Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial") and Rutgeerts et al. (2005, "Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis").
Paper Timeline
Most-cited paper highlighted in red. Papers ordered chronologically.
Advanced Directions
Recent preprints explore immune-related actinopathies linking immunodeficiency, autoimmunity, and autoinflammation via actin cytoskeleton defects. Progress in primary immunodeficiencies highlights improved diagnosis and treatment of inborn errors of immunity with autoimmune manifestations. FDA reviews of leniolisib for pediatric APDS indicate ongoing refinements in immunodeficiency therapies.
Papers at a Glance
| # | Paper | Year | Venue | Citations | Open Access |
|---|---|---|---|---|---|
| 1 | Reciprocal developmental pathways for the generation of pathog... | 2006 | Nature | 6.8K | ✕ |
| 2 | A frameshift mutation in NOD2 associated with susceptibility t... | 2001 | Nature | 5.0K | ✓ |
| 3 | IL-17 and Th17 Cells | 2009 | Annual Review of Immun... | 4.7K | ✕ |
| 4 | Immunobiology: the immune system in health and disease | 1995 | Choice Reviews Online | 4.1K | ✕ |
| 5 | Maintenance infliximab for Crohn's disease: the ACCENT I rando... | 2002 | The Lancet | 4.1K | ✕ |
| 6 | IL-23 drives a pathogenic T cell population that induces autoi... | 2005 | The Journal of Experim... | 4.0K | ✓ |
| 7 | Infliximab for Induction and Maintenance Therapy for Ulcerativ... | 2005 | New England Journal of... | 3.8K | ✓ |
| 8 | TGFβ in the Context of an Inflammatory Cytokine Milieu Support... | 2006 | Immunity | 3.5K | ✓ |
| 9 | <i>LMO2</i> -Associated Clonal T Cell Proliferation in Two Pat... | 2003 | Science | 3.5K | ✕ |
| 10 | Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia | 2000 | New England Journal of... | 3.3K | ✕ |
In the News
Pharming Group receives Complete Response Letter from ...
Release SummaryPharming Group received an FDA Complete Response Letter for its sNDA for Joenja® (leniolisib) in children aged 4–11 with APDS Company ProfilePharming Group N.V.Industry:Pharmaceutica...
FDA knocks back Pharming's bid for wider Joenja use
**The FDA has turned down an attempt by Pharming to broaden the label of its Joenja drug for a rare immunodeficiency disorder so it can be used in younger patients.**
AGC Biologics Partners with Rarity PBC to Advance Life ...
RDP-101, for Adenosine Deaminase Severe Combined Immunodeficiency Disorder.
Supplemental NDA for leniolisib accepted for children with ...
The FDA has accepted Pharming Group’s supplemental new drug application for leniolisib in treating activated phosphoinositide 3-kinase delta syndrome, or APDS, in children aged 4 to 11 years, accor...
Foundation sends letter opposing research cuts
# Foundation sends letter opposing research cuts June 16, 2025
Code & Tools
Pyrepseq is`scipy`&`seaborn`for studying adaptive immunity: modular implementations of algorithms for fast analyses, and bespoke plotting functions...
## Repository files navigation # AIFI Immune Health Atlas Generation
Single-cell sequencing is an emerging technology in the field of immunology and oncology that allows researchers to couple RNA quantification and o...
LIgO is a tool for simulation of adaptive immune receptors and repertoires,
This repo keeps the reproducible analysis pipeline of our manuscript "Global immune repertoire profiling suggests multifaceted unresolved dysregula...
Recent Preprints
Immune-related actinopathies at the cross-road of immunodeficiency, autoimmunity and autoinflammation
Actin cytoskeleton remodelling drives the migration of immune cells and their engagement in dynamic cell–cell contacts. The importance of actin cytoskeleton dynamics in immune cell function is high...
Progress in Diagnosis and Treatment of Primary ...
Primary immunodeficiencies (PIDs), or elsealso called inborn errors of immunity, are a heterogenous group of genetic disorders characterized by immune system dysfunction. They are usually associate...
Immunodeficiency and Autoimmunity
Webpage updated May 2025
Immunodeficiencies in Adults: Key Considerations for ...
Immunodeficiencies in adults are increasingly recognized yet often remain underdiagnosed, leading to significant morbidity from recurrent infections, autoimmunity, and malignancy. Both primary immu...
Immunological disorders - Latest research and news
Definition Immunological disorders are diseases or conditions caused by a dysfunction of the immune system and include allergy, asthma, autoimmune diseases, autoinflammatory syndromes and immunolog...
Latest Developments
Recent developments in immunodeficiency and autoimmune disorders research include innovative treatments such as resetting 'rogue' immune cells to manage autoimmune diseases like rheumatoid arthritis, lupus, and multiple sclerosis (PBS News, published 11/13/2025), advancements in immunotherapy including CAR-T cell therapies showing promising remission results (Nature, published 11/26/2025), and ongoing clinical trials exploring targeted CAR-T approaches for refractory autoimmune conditions (Nature Medicine, published 09/24/2025; and Nature Medicine, published 01/07/2026). Additionally, Nobel laureates have identified immune regulation mechanisms, such as peripheral immune tolerance, which are fundamental to understanding and treating these disorders (NobelPrize.org, published 10/06/2025).
Sources
Frequently Asked Questions
What role do Th17 cells play in autoimmune disorders?
Th17 cells produce IL-17 and drive pathogenic inflammation in autoimmune diseases. Bettelli et al. (2006) showed reciprocal developmental pathways generate pathogenic effector Th17 and regulatory T cells. Korn et al. (2009) detailed how CD4+ T cells differentiate into IL-17-producing Th17 subsets with distinct effector functions.
How does IL-23 contribute to autoimmune inflammation?
IL-23 drives a pathogenic T cell population inducing autoimmune inflammation, distinct from IL-12's role in Th1 cells. Langrish et al. (2005) demonstrated IL-23, composed of p19 and p40 subunits, promotes this population. This pathway is central to disorders like those studied in Crohn's disease susceptibility.
What is the genetic link between NOD2 mutations and Crohn's disease?
A frameshift mutation in NOD2 associates with susceptibility to Crohn's disease. Ogura et al. (2001) identified this mutation in "A frameshift mutation in NOD2 associated with susceptibility to Crohn's disease". It highlights genetic factors in immunodeficiency-related autoimmunity.
What risks arise from gene therapy in SCID-X1?
Gene therapy for SCID-X1 corrected γc deficiency in 9 of 10 patients but caused LMO2-associated clonal T cell proliferation in two. Hacein-Bey-Abina et al. (2003) reported this in "LMO2-Associated Clonal T Cell Proliferation in Two Patients after Gene Therapy for SCID-X1". It demonstrates both efficacy and leukemogenic risks.
How effective is infliximab in ulcerative colitis?
Infliximab at weeks 0, 2, 6, and every eight weeks increased clinical response rates at weeks 8, 30, and 54 versus placebo in moderate-to-severe ulcerative colitis. Rutgeerts et al. (2005) confirmed this in "Infliximab for Induction and Maintenance Therapy for Ulcerative Colitis". ClinicalTrials.gov numbers NCT00036439 and NCT00096655 support these findings.
What are key genomic predictors in chronic lymphocytic leukemia?
Genomic aberrations in chronic lymphocytic leukemia independently predict disease progression and survival. Döhner et al. (2000) established this in "Genomic Aberrations and Survival in Chronic Lymphocytic Leukemia". These inform risk-adapted treatment strategies.
Open Research Questions
- ? How can the balance between pathogenic Th17 and regulatory T cells be therapeutically modulated to prevent autoimmune inflammation?
- ? What mechanisms underlie NOD2 frameshift mutations leading to Crohn's disease susceptibility?
- ? How does IL-23 specifically drive pathogenic T cells without promoting Th1 development?
- ? What factors trigger LMO2-associated clonal proliferation following SCID-X1 gene therapy?
- ? Which genomic aberrations most accurately predict survival in chronic lymphocytic leukemia?
Recent Trends
Preprints from the last six months emphasize actin-regulatory defects in immune-related actinopathies at the intersection of immunodeficiency, autoimmunity, and autoinflammation.
Advances in primary immunodeficiencies note associations with recurrent infections and autoimmune manifestations.
FDA accepted a supplemental NDA for leniolisib in children aged 4-11 with APDS but issued a Complete Response Letter for Joenja expansion.
Research Immunodeficiency and Autoimmune Disorders with AI
PapersFlow provides specialized AI tools for your field researchers. Here are the most relevant for this topic:
AI Literature Review
Automate paper discovery and synthesis across 474M+ papers
Deep Research Reports
Multi-source evidence synthesis with counter-evidence
Paper Summarizer
Get structured summaries of any paper in seconds
AI Academic Writing
Write research papers with AI assistance and LaTeX support
Start Researching Immunodeficiency and Autoimmune Disorders with AI
Search 474M+ papers, run AI-powered literature reviews, and write with integrated citations — all in one workspace.