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Atlas / Disease / immunoglobulin G4-related sclerosing disease

immunoglobulin G4-related sclerosing disease

disease
On this page

Also known as hyper-IgG4 diseaseIgG4-associated diseaseIgG4-positive multiorgan lymphoproliferative syndromeIgG4-RDIgG4-related autoimmune diseaseIgG4-related diseaseIgG4-related sclerosing diseaseIgG4-related systemic diseaseIgG4-related systemic sclerosing diseaseIgG4-syndromemultifocal fibrosclerosismultifocal idiopathic fibrosclerosissystemic IgG4-related plasmacytic syndromesystemic IgG4-related sclerosing syndrome

Summary

immunoglobulin G4-related sclerosing disease (MONDO:0017287) is a disease (an umbrella term covering 14 Mondo subtypes) with 30 GWAS associations across 3 studies and 45 clinical trials. Top therapeutic interventions include belimumab, diphenhydramine, and efgartigimod alfa. A subtype of autoimmune disease — broader associated-gene and molecular evidence is on the parent page (see Disease family below).

At a glance

  • Prevalence: Unknown (Worldwide) [Orphanet-validated]
  • Umbrella term: 14 Mondo subtypes
  • GWAS associations: 30
  • Phenotypes (HPO): 30
  • Clinical trials: 45

Clinical features

Epidemiology

Prevalence records

4 prevalence record(s), Orphanet:

TypeClassValueGeographyValidation
Annual incidence1-9 / 100 0001.026JapanValidated
Annual incidence1-9 / 1 000 0000.6885DenmarkValidated
Point prevalence1-9 / 100 000JapanValidated
Point prevalence1-9 / 1 000 0000.576DenmarkValidated

Signs & symptoms

Clinical features (HPO)

30 HPO clinical features (Orphanet curated; top 30 by frequency):

HPO IDTermFrequency
HP:0000872Hashimoto thyroiditisFrequent (30-79%)
HP:0001733PancreatitisFrequent (30-79%)
HP:0003493Antinuclear antibody positivityFrequent (30-79%)
HP:0005200Retroperitoneal fibrosisFrequent (30-79%)
HP:0005421Decreased circulating complement C3 concentrationFrequent (30-79%)
HP:0030991Sclerosing cholangitisFrequent (30-79%)
HP:0030992Abnormal pancreatic duct morphologyFrequent (30-79%)
HP:0031281SialadenitisFrequent (30-79%)
HP:0032300Increased circulating IgG4 levelFrequent (30-79%)
HP:0045042Decreased circulating complement C4 concentrationFrequent (30-79%)
HP:0000315Abnormality of the orbital regionFrequent (30-79%)
HP:0002923Rheumatoid factor positiveOccasional (5-29%)
HP:0003212Increased circulating IgE levelOccasional (5-29%)
HP:0003237Increased circulating IgG levelOccasional (5-29%)
HP:0003565Elevated erythrocyte sedimentation rateOccasional (5-29%)
HP:0005339Abnormality of complement systemOccasional (5-29%)
HP:0011227Elevated circulating C-reactive protein concentrationOccasional (5-29%)
HP:0001744SplenomegalyExcluded (0%)
HP:0001873ThrombocytopeniaExcluded (0%)
HP:0001880EosinophiliaExcluded (0%)
HP:0001882LeukopeniaExcluded (0%)
HP:0001945FeverExcluded (0%)
HP:0032229Perinuclear antineutrophil antibody positivityExcluded (0%)
HP:0032235Anti-La/SS-B antibody positivityExcluded (0%)
HP:0033028Anti-U1 ribonucleoprotein antibody positivityExcluded (0%)
HP:0033040Anti-Sm antibody positivityExcluded (0%)
HP:0033555Anti-Ro/SS-A antibody positivityExcluded (0%)
HP:0100280Crohn’s diseaseExcluded (0%)
HP:0100778CryoglobulinemiaExcluded (0%)
HP:0032252GranulomaVery rare (<1-4%)

Identifiers

Disease identifiers

FieldValue
Canonical nameimmunoglobulin G4-related sclerosing disease
Mondo IDMONDO:0017287
Orphanet284264, 596448
DOIDDOID:0080356
ICD-1199883782
NCITC95992
UMLSC3203653
MedGen473761
GARD0012521
MedDRA10071569
Is cancer (heuristic)no

Also known as: hyper-IgG4 disease · IgG4-associated disease · IgG4-positive multiorgan lymphoproliferative syndrome · IgG4-RD · IgG4-related autoimmune disease · IgG4-related disease · IgG4-related sclerosing disease · IgG4-related systemic disease · IgG4-related systemic sclerosing disease · IgG4-syndrome · immunoglobulin G4-related sclerosing disease · multifocal fibrosclerosis · multifocal idiopathic fibrosclerosis · systemic IgG4-related plasmacytic syndrome · systemic IgG4-related sclerosing syndrome

Data availability: 30 GWAS associations (3 studies) · 6 cell lines.

Disease family

This is a subtype of autoimmune disease. Genetic, therapeutic, and trial evidence is largely curated at the broader-term level — see the parent page for the associated-gene cohort and molecular evidence.

Classification path: disease › human disease › disease by body system or component › immune system disorder › autoimmune disease › immunoglobulin G4-related sclerosing disease

Related subtypes (46): autoimmune disease, multisystem, infantile-onset, autoimmune disorder of endocrine system, autoimmune disorder of exocrine system, autoimmune disease of ear, nose and throat, autoimmune disorder of gastrointestinal tract, autoimmune disorder of musculoskeletal system, autoimmune disorder of blood, autoimmune disorder of cardiovascular system, phacolytic glaucoma, Jaccoud syndrome, autoimmune disorder of the nervous system, lupus erythematosus, anti-neutrophil antibody associated vasculitis, cryoglobulinemia, CNS demyelinating autoimmune disease, type III hypersensitivity disease, vitiligo, anti-glomerular basement membrane disease, autoimmune pulmonary alveolar proteinosis, Reynolds syndrome, overlapping connective tissue disease, tempi syndrome, rheumatic fever, autoerythrocyte sensitization syndrome, autoimmune lymphoproliferative syndrome, secondary neonatal autoimmune disease, euthyroid Graves orbitopathy, Kimura disease, autoimmune thrombocytopenia, autoimmune bullous skin disease, scleroderma, Susac syndrome, undifferentiated connective tissue syndrome, type II hypersensitivity reaction disease, autoimmune urticaria, autoimmune glomerulonephritis, multisystem autoimmune disease due to IKAROS gain of function, autoimmune pulmonary disease due to PD-1 deficiency, non-specific autoimmune supratentorial encephalitis with characteristic antibodies, non-specific autoimmune supratentorial encephalitis without characteristic antibodies, non-specific autoimmune brainstem encephalitis with characteristic antibodies, non-specific autoimmune brainstem encephalitis without characteristic antibodies, non-specific autoimmune cerebellar ataxia with characteristic antibodies, non-specific autoimmune cerebellar ataxia without characteristic antibodies, autoimmune disease with susceptibility to mycobacterium tuberculosis, antiphospholipid syndrome

Subtypes (14): autoimmune pancreatitis, IgG4-related mesenteritis, IgG4-related sclerosing cholangitis, IgG4-related kidney disease, IgG4-related aortitis, IgG4-related pachymeningitis, IgG4-related submandibular gland disease, IgG4-related ophthalmic disorder, eosinophilic angiocentric fibrosis, primary cutaneous plasmacytosis, cutaneous pseudolymphoma, IgG4-related retroperitoneal fibrosis, IgG4-related mediastinitis, IgG4-related thyroid disease

Genetics & variants

GWAS landscape

30 GWAS associations across 3 studies. Top hits map to 13 distinct genes (as reported by GWAS).

Top associations by p-value

rsIDp-valueGeneRisk alleleOdds ratio
rs38887773e-96PRR3A3.44
rs78020392e-85EVA1CP3 - ALG1L5PT3.42
rs1500487566e-80TPTE2A8.67
rs25374313e-65DTX2P1-UPK3BP1-PMS2P11, FAM185BPG2.89
rs14535361e-44OR4D10 - OR4D8PT2.1
rs283712513e-44HLA-DQB1 - MTCO3P1T1.85
rs1175619333e-39C4BPAP1 - C4BPAP2T3.22
rs732372164e-38MDGA2A5.41
rs1132570321e-36LINC02966T1.93
rs572352332e-34GRIN3AA3.78
HLA-B*08012e-33?4.63
HLA-DRB1*09012e-32?0.37
rs92707722e-32HLA-DRB1 - HLA-DQA1T1.7
rs3900421e-29LINC01783 - PDE4DIPP8G1.69
rs60665768e-29LINC01523, LINC01522T2.03
HLA-B*46011e-27?0.34
rs6363293e-25NBPF12 - RNU1-151PT0.59
rs13409767e-25RPL31P11, RPL31P11C1.59
HLA-DQB1*06023e-24?1.92
rs47171562e-21CICP24 - GABPAPG1.71
rs351811274e-19RPS23P9 - FCGR3BG1.49
rs93488781e-11FKBPL - PPT2G0.67
HLA-B*40015e-11?0.56
HLA-DRB1*047e-11?1.49
rs133764851e-10FCGR2BA0.59
rs95599152e-10SPACA7BPT1.33
rs1163536922e-10HLA-DRB9 - HLA-DRB5C0.54
rs22339641e-08C6orf15 - PSORS1C1G0.74
rs342129235e-08HLA-DRB1 - HLA-DQA1?

Top studies (by case count)

StudyLead authorYearCasesControlsTitle
GCST90728686Yan S20251,97212,236Genome-wide association studies reveal new insights into the genetic basis of IgG4-related disease in the Chinese Han population.
GCST90728685Yan S20251,11510,154Genome-wide association studies reveal new insights into the genetic basis of IgG4-related disease in the Chinese Han population.
GCST90728621Zhang YO20258692,659IgG4-related disease in the Japanese population: a whole-genome sequencing study.

Variant details and genetic-evidence tiers

Tier distribution (top 50 variants)

TierVariants
Tier 1: coding0
Tier 2: splice/UTR0
Tier 3: regulatory0
Tier 4: intronic/intergenic29

MAF distribution

BucketVariants
common (>=0.05)22
low_freq (0.01-0.05)0
rare (<0.01)0
unknown7

Functional consequences

ConsequenceCount
intron_variant15
intergenic_variant7
unknown6
synonymous_variant1

Top variants

rsIDChrPosAllelesMAFConsequenceGenep-valueTier
rs3888777630562039G>A0.05synonymous_variantPRR33e-96Tier 4: intronic/intergenic
rs780203976907654A>T0.05intron_variantEVA1CP3 - ALG1L5P2e-85Tier 4: intronic/intergenic
rs1500487561319517545G>A,T0.05intron_variantTPTE26e-80Tier 4: intronic/intergenic
rs2537431777097677G>A,C0.05intron_variantDTX2P1-UPK3BP1-PMS2P11, FAM185BP3e-65Tier 4: intronic/intergenic
rs14535361159481839T>A,C0.05intergenic_variantOR4D10 - OR4D8P1e-44Tier 4: intronic/intergenic
rs28371251632685241T>C0.05intergenic_variantHLA-DQB1 - MTCO3P13e-44Tier 4: intronic/intergenic
rs1175619331207198479G>C,Tintron_variantC4BPAP1 - C4BPAP23e-39Tier 4: intronic/intergenic
rs732372161446933586T>A0.05intron_variantMDGA24e-38Tier 4: intronic/intergenic
rs1132570322113365940C>T0.05intron_variantLINC029661e-36Tier 4: intronic/intergenic
rs572352339101657636G>A0.05intron_variantGRIN3A2e-34Tier 4: intronic/intergenic
HLA-B*08012e-33Tier 4: intronic/intergenic
HLA-DRB1*09012e-32Tier 4: intronic/intergenic
rs9270772632601190T>A,C0.05intergenic_variantHLA-DRB1 - HLA-DQA12e-32Tier 4: intronic/intergenic
rs390042116543405G>A,C0.05intergenic_variantLINC01783 - PDE4DIPP81e-29Tier 4: intronic/intergenic
rs60665762047983794T>A,G0.05intron_variantLINC01523, LINC015228e-29Tier 4: intronic/intergenic
HLA-B*46011e-27Tier 4: intronic/intergenic
rs6363291147070664T>A,C,G0.05intron_variantNBPF12 - RNU1-151P3e-25Tier 4: intronic/intergenic
rs13409761161691699C>A,G0.05intron_variantRPL31P11, RPL31P117e-25Tier 4: intronic/intergenic
HLA-DQB1*06023e-24Tier 4: intronic/intergenic
rs4717156763889095T>G0.05intron_variantCICP24 - GABPAP2e-21Tier 4: intronic/intergenic
rs351811271161620953A>C,G,T0.05intron_variantRPS23P9 - FCGR3B4e-19Tier 4: intronic/intergenic
rs9348878632141517A>G0.05intergenic_variantFKBPL - PPT21e-11Tier 4: intronic/intergenic
HLA-B*40015e-11Tier 4: intronic/intergenic
HLA-DRB1*047e-11Tier 4: intronic/intergenic
rs133764851161676087G>A,C0.232intron_variantFCGR2B1e-10Tier 4: intronic/intergenic
rs955991513110967285T>A,C0.05intron_variantSPACA7BP2e-10Tier 4: intronic/intergenic
rs116353692632476291A>C0.05intron_variantHLA-DRB9 - HLA-DRB52e-10Tier 4: intronic/intergenic
rs2233964631113142A>G0.05intergenic_variantC6orf15 - PSORS1C11e-08Tier 4: intronic/intergenic
rs34212923632592706T>C0.05intergenic_variantHLA-DRB1 - HLA-DQA15e-08Tier 4: intronic/intergenic

Genes & proteins

No associated-gene cohort resolved for this disease. Atlas builds the molecular and therapeutic sections — associated genes, protein families, druggability, pathways, interactions, and drug associations — by aggregating over a disease’s associated genes (resolved via GWAS / GenCC / ClinVar / CIViC), and none resolved here. This is expected for antibody-mediated, autoimmune, or otherwise non-gene-defined conditions; the curated evidence for this disease is its clinical features, GWAS susceptibility, and clinical trials (above).

Function

No pathway enrichment — requires an associated-gene cohort.

Therapeutics

No druggable-target or therapeutic data for this disease’s cohort.

Clinical trials & evidence

Clinical trials

Clinical trials: 45.

Phase distribution (across all retrieved trials)

PhaseTrials
Not specified20
PHASE28
PHASE14
EARLY_PHASE14
PHASE43
PHASE2/PHASE33
PHASE32
PHASE1/PHASE21

Top trials by phase / activity

NCTPhaseStatusTitle
NCT02703194PHASE4COMPLETEDLeflunomide for Maintenance of Remission in IgG4 Related Disease
NCT03368274PHASE4UNKNOWNTo Evaluate the Clinical Efficacy of Iguratimod in the Treatment of IgG4 Related Disease (IgG4-RD) With Mild Symptom
NCT04660565PHASE4UNKNOWNBelimumab Treatment for IgG4-related Disease
NCT04540497PHASE3ACTIVE_NOT_RECRUITINGA Study of Inebilizumab Efficacy and Safety in IgG4- Related Disease
NCT05662241PHASE3ACTIVE_NOT_RECRUITINGA Phase 3 Study of Obexelimab in Patients With IgG4-Related Disease
NCT07068165PHASE2/PHASE3RECRUITINGA Randomized Controlled Study of the Efficacy and Safety of Lenalidomide in the Treatment of Active IgG4-related Disease
NCT07535554PHASE2/PHASE3RECRUITINGThe Investigators Will Evaluate the Diagnostic Performance of [18F]-AlF-FAPI-74 PET/CT in Inflammatory Disorders and Compare it With the Current Gold Standard for Inflammation, FDG PET/CT, in Three Patient Cohort: Patients Presenting With Fever of Unknown Origin, IgG4-RD and AxSpA.
NCT01758393PHASE2/PHASE3UNKNOWNGlucocorticoids in Patients With IgG4-RD
NCT06285539PHASE2RECRUITINGDrug Rediscovery for Rare Immune Mediated Inflammatory Diseases
NCT06794008PHASE2RECRUITINGBCMA-CD19 CAR-T Therapy for Refractory Autoimmune Diseases
NCT07025330PHASE2RECRUITINGA Study of Efgartigimod in Patients With IgG4-Related Disease
NCT07061938PHASE1/PHASE2RECRUITINGStudy to Assess Safety, Efficacy and Persistence of ACE1831, in Subjects With IgG4-Related Disease
NCT07148791PHASE2RECRUITINGExploratory Study of Anti-BCMA-CD19 CAR-T Cell Therapy in Relapsed or Refractory IgG4-Related Disease
NCT02725476PHASE2COMPLETEDStudy to Evaluate the Effect of XmAb®5871 on Disease Activity in Patients With IgG4-Related Disease (RD)
NCT03669861PHASE2COMPLETEDSafety and Efficacy of Abatacept in IgG4-Related Disease
NCT04602598PHASE2COMPLETEDZanubrutinib in Patients With IgG4-Related Disease
NCT04918147PHASE2TERMINATEDElotuzumab in Immunoglobulin G4-Related Disease (IgG4-RD)
NCT06285279PHASE1RECRUITINGThe BCMA/CD19 Dual Targeted CAR-T Cell in Participants With Autoimmune Kidney Diseases
NCT06978647PHASE1RECRUITINGA Clinical Study of YTS109 Cell in R/R Autoimmune Diseases
NCT06978738PHASE1NOT_YET_RECRUITINGUCAR T-cell Therapy Targeting CD19/ BCMA in Patients With Relapse/ Refractory Autoimmune Diseases
NCT02705638PHASE1COMPLETEDTreatment of IgG4-Related Disease With Revlimid and Rituximab
NCT06497361EARLY_PHASE1RECRUITINGSafety and Efficacy of PRG-2311 for Refractory Lupus Nephritis and IgG4-Related Disease
NCT06497387EARLY_PHASE1RECRUITINGSafety and Efficacy of PRG-1801 for Refractory Lupus Nephritis and IgG4-Related Disease
NCT07298590EARLY_PHASE1NOT_YET_RECRUITINGAn Exploratory Clinical Study on the Safety and Efficacy of CD19/BCMA CAR-NK in the Treatment of Relapsed and Refractory IgG4-related Disease
NCT04125511EARLY_PHASE1UNKNOWNCharacterizing IgG4-RD With 68Ga-FAPI PET/CT
NCT01670695Not specifiedRECRUITINGA Prospective Cohort Study of IgG4RD in China
NCT03023371Not specifiedRECRUITINGNational Registry of IgG4-RD in China
NCT03473912Not specifiedRECRUITINGMeir Medical Center Rheumatologic Biobank
NCT05746689Not specifiedNOT_YET_RECRUITINGStudy of Sirolimus in IgG4-related Disease
NCT06655831Not specifiedNOT_YET_RECRUITINGKey Mechanisms of Abnormal T Cell Activation and Differentiation in IgG4-Related Ophthalmic Disease
NCT06663618Not specifiedRECRUITINGShort-term Glucocorticoid Combined with MMF for IgG4-RD
NCT06696027Not specifiedRECRUITINGAYLo - AutoimmunitY and Loss of y
NCT06844864Not specifiedACTIVE_NOT_RECRUITINGAdaptive and Trained Immunity in the Pathogenesis of IgG4-Related Disease
NCT07104058Not specifiedRECRUITINGA Study on the Effect of MRD Detected by FAPI PET / CT on the Recurrence of IgG4-RD
NCT07536841Not specifiedRECRUITINGValidation of the Odesa Criteria 2026 for Autoimmune Pancreatitis
NCT07593911Not specifiedNOT_YET_RECRUITINGA Study to Evaluate MTM-H-001 Injection in Adult Patients With B-Cell-Related Autoimmune Diseases
NCT02616705Not specifiedCOMPLETEDBile Usefulness for Detecting IgG4-related Sclerosing Cholangitis
NCT02899039Not specifiedCOMPLETEDFollicular Helper T Cells: Biological Marker and Involvement in the Physiopathology of the IgG4-related Disease
NCT03267875Not specifiedUNKNOWNA Laboratory Scan of Patients With Aortic Aneurysms to IgG4 Levels in the Blood
NCT03466970Not specifiedUNKNOWNPlasmablast Detection From IgG4-Related Disease Patients

Drugs tested across these trials (top 30)

MoleculeMax phaseTrials referencing
BELIMUMAB41
DIPHENHYDRAMINE41
EFGARTIGIMOD ALFA41
ELOTUZUMAB41
FAMOTIDINE41
FILGOTINIB41
INEBILIZUMAB41
LEFLUNOMIDE41
PREDNISONE41
ZANUBRUTINIB41
OBEXELIMAB32
STAPOKIBART31
FAPI GA-6821
CHEMBL1572005
CHEMBL519312801

About this page

Generated deterministically by Sugi Atlas from primary biomedical databases via BioBTree. Every record on this page traces to a primary source.

Generated
Atlas version
v1.1.2
BioBTree
v2.0.2

Sources 23

This page pulls from 23 datasets indexed by BioBTree:

chembl_moleculecivic_evidenceclinical_trialsclinvardbsnpdoidefogardgenccgwasgwas_studyhgncicd11meddramedgenmeshmimmondomondochildmondoparentncitorphanetumls