Role of the Complement Pathway in Inflammatory Skin Diseases: A Focus on Hidradenitis Suppurativa.

Although the role of immune dysregulation in hidradenitis suppurativa (HS) has yet to be elucidated, recent studies identified several complement abnormalities in patients with HS. The complement system serves a critical role in the modulation of immune response and regulation of cutaneous commensal bacteria. Complement is implicated in several inflammatory skin diseases including systemic lupus erythematosus, angioedema, pemphigus, bullous pemphigoid, and HS. A model of HS pathogenesis is proposed, integrating the role of commensal bacteria, cutaneous immune responses, and complement dysregulation. The role of complement in disease pathogenesis has led to the development of novel anticomplement agents and clinical trials investigating the efficacy of such treatments in HS.

• Publication year

  2019

• Venue

  Journal of Investigative Dermatology

• Publication date

  2019-12-20

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.jid.2019.09.009PMID 31870626
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Are Bacteria Infectious Pathogens in Hidradenitis Suppurativa? Debate at the Symposium for Hidradenitis Suppurativa Advances Meeting, November 2017.

  2019cited by this paper
• Contribution of fibroblasts to tunnel formation and inflammation in hidradenitis suppurativa/ acne inversa

  2019cited by this paper
• The skin transcriptome in hidradenitis suppurativa uncovers an antimicrobial and sweat gland gene signature which has distinct overlap with wounded skin

  2019cited by this paper
• The microbiome of tunnels in hidradenitis suppurativa patients

  2019cited by this paper
• North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part II: Topical, intralesional, and systemic medical management.

  2019cited by this paper
• Defining lesional, perilesional and unaffected skin in hidradenitis suppurativa: proposed recommendations for clinical trials and translational research studies

  2019cited by this paper
• North American clinical management guidelines for hidradenitis suppurativa: A publication from the United States and Canadian Hidradenitis Suppurativa Foundations: Part I: Diagnosis, evaluation, and the use of complementary and procedural management.

  2019cited by this paper
• Ravulizumab: a complementary option for PNH.

  2019cited by this paper
• Biologics for hidradenitis suppurativa: an update.

  2019cited by this paper
• Topical, systemic and biologic therapies in hidradenitis suppurativa: pathogenic insights by examining therapeutic mechanisms

  2019cited by this paper
• Ravulizumab: First Global Approval

  2019cited by this paper
• British Association of Dermatologists guidelines for the management of hidradenitis suppurativa (acne inversa) 2018

  2019influential reference
• Ravulizumab (ALXN1210) vs eculizumab in adult patients with PNH naive to complement inhibitors: the 301 study.

  2019cited by this paper
• Ravulizumab (ALXN1210) vs eculizumab in C5-inhibitor-experienced adult patients with PNH: the 302 study.

  2019cited by this paper
• A systematic review and critical evaluation of inflammatory cytokine associations in hidradenitis suppurativa

  2018cited by this paper
• Complement Activation in Inflammatory Skin Diseases

  2018cited by this paper
• Hidradenitis Suppurativa: A Systematic Review Integrating Inflammatory Pathways Into a Cohesive Pathogenic Model

  2018cited by this paper
• Increasing the Complement of Therapeutic Options in Bullous Pemphigoid.

  2018cited by this paper
• Population‐based Clinical Practice Research Datalink study using algorithm modelling to identify the true burden of hidradenitis suppurativa

  2018cited by this paper
• Complement in glomerular diseases

  2018cited by this paper
• Integrating the skin and blood transcriptomes and serum proteome in hidradenitis suppurativa reveals complement dysregulation and a plasma cell signature

  2018cited by this paper
• Expanding Complement Therapeutics for the Treatment of Paroxysmal Nocturnal Hemoglobinuria.

  2018cited by this paper
• The inflammatory effects of TNF-α and complement component 3 on coagulation

  2018cited by this paper
• Complement activation in hidradenitis suppurativa: a new pathway of pathogenesis?

  2018influential reference
• The Role of Skin and Orogenital Microbiota in Protective Immunity and Chronic Immune-Mediated Inflammatory Disease

  2018cited by this paper
• Complement in the Initiation and Evolution of Rheumatoid Arthritis

  2018cited by this paper
• Development and validation of a LC-MS/MS assay for pharmacokinetic studies of complement C5a receptor antagonists PMX53 and PMX205 in mice

  2018cited by this paper
• Targeted treatments for hidradenitis suppurativa: a review of the current literature and ongoing clinical trials

  2018cited by this paper
• Innate antimicrobial immunity in the skin: A protective barrier against bacteria, viruses, and fungi

  2018cited by this paper
• Skin microbiota–host interactions

  2018cited by this paper
• Investigational drugs in clinical trials for Hidradenitis Suppurativa

  2018cited by this paper
• Accelerated Aging and Clearance of Host Anti-inflammatory Enzymes by Discrete Pathogens Fuels Sepsis.

  2018cited by this paper
• Lipocalin‐2 is expressed by activated granulocytes and keratinocytes in affected skin and reflects disease activity in acne inversa/hidradenitis suppurativa

  2017cited by this paper
• A systematic review and critical evaluation of reported pathogenic sequence variants in hidradenitis suppurativa

  2017cited by this paper
• Complement in ANCA-associated vasculitis: mechanisms and implications for management

  2017cited by this paper
• Therapeutic Inhibition of Complement: Well Worth the Risk.

  2017cited by this paper
• Pathways leading to an immunological disease: systemic lupus erythematosus

  2017cited by this paper
• Novel mechanisms and functions of complement

  2017cited by this paper
• Complement C3 Exacerbates Imiquimod-Induced Skin Inflammation and Psoriasiform Dermatitis

  2017cited by this paper
• Randomized Trial of C5a Receptor Inhibitor Avacopan in ANCA-Associated Vasculitis.

  2017cited by this paper
• Pathophysiology of hidradenitis suppurativa

  2017cited by this paper
• The role of the complement system in hereditary angioedema.

  2017cited by this paper
• Controlling the anaphylatoxin C5a in diseases requires a specifically targeted inhibition.

  2017cited by this paper
• The Follicular Skin Microbiome in Patients With Hidradenitis Suppurativa and Healthy Controls

  2017cited by this paper
• CD46 Activation Regulates miR-150–Mediated Control of GLUT1 Expression and Cytokine Secretion in Human CD4+ T Cells

  2016cited by this paper
• A novel “complement–metabolism–inflammasome axis” as a key regulator of immune cell effector function

  2016cited by this paper
• TNF Regulates Essential Alternative Complement Pathway Components and Impairs Activation of Protein C in Human Glomerular Endothelial Cells

  2016cited by this paper
• Hereditary and acquired C1-inhibitor-dependent angioedema: from pathophysiology to treatment

  2016cited by this paper
• Mechanisms of Disease: Pemphigus and Bullous Pemphigoid.

  2016cited by this paper
• Complement-Mediated Regulation of Metabolism and Basic Cellular Processes.

  2016cited by this paper
• Koch's postulates, microbial dysbiosis and inflammatory bowel disease.

  2016cited by this paper
• Intrinsic Defect in Keratinocyte Function Leads to Inflammation in Hidradenitis Suppurativa.

  2016cited by this paper
• Compartmentalized Cytokine Responses in Hidradenitis Suppurativa

  2015cited by this paper
• C5aR, TNF-α, and FGL2 contribute to coagulation and complement activation in virus-induced fulminant hepatitis.

  2015cited by this paper
• Complement System in Dermatological Diseases – Fire Under the Skin

  2015cited by this paper
• Complement Deficiency Promotes Cutaneous Wound Healing in Mice

  2015cited by this paper
• Complement, a target for therapy in inflammatory and degenerative diseases

  2015cited by this paper
• Complement regulator CD46: genetic variants and disease associations

  2015cited by this paper
• Dysbiosis and Staphylococcus aureus Colonization Drives Inflammation in Atopic Dermatitis.

  2015cited by this paper
• The intestinal microbiota: its role in health and disease

  2015cited by this paper
• Bacterial Pathogens Associated with Hidradenitis Suppurativa, France

  2014cited by this paper
• Inflammaging in Skin and Other Tissues - The Roles of Complement System and Macrophage

  2014cited by this paper
• Complement modulation of T cell immune responses during homeostasis and disease

  2014cited by this paper
• Genetic and Intervention Studies Implicating Complement C3 as a Major Target for the Treatment of Periodontitis

  2014cited by this paper
• The complement system in systemic lupus erythematosus: an update

  2014cited by this paper
• Dialogue between skin microbiota and immunity

  2014cited by this paper
• Dynamics of complement activation in aHUS and how to monitor eculizumab therapy.

  2014cited by this paper
• Complement modulates the cutaneous microbiome and inflammatory milieu

  2013cited by this paper
• Terminal complement inhibitor eculizumab in atypical hemolytic-uremic syndrome.

  2013cited by this paper
• Meningococcal disease and the complement system

  2013cited by this paper
• CD46: the 'multitasker' of complement proteins.

  2013cited by this paper
• Myeloid marker S100A8/A9 and lymphocyte marker, soluble interleukin 2 receptor: biomarkers of hidradenitis suppurativa disease activity?

  2013cited by this paper
• Complement system in psoriatic arthritis: a useful marker in response prediction and monitoring of anti-TNF treatment.

  2012cited by this paper
• Protease-dependent mechanisms of complement evasion by bacterial pathogens

  2012cited by this paper
• Specific Inhibition of Complement Activation Significantly Ameliorates Autoimmune Blistering Disease in Mice

  2011cited by this paper
• Complement System and Rheumatoid Arthritis: Relationships with Autoantibodies, Serological, Clinical Features, and Anti-TNF Treatment

  2011cited by this paper
• Porphyromonas gingivalis mediates the shedding and proteolysis of complement regulatory protein CD46 expressed by oral epithelial cells.

  2009cited by this paper
• Interactions between Neisseria meningitidis and the complement system.

  2007cited by this paper
• Association between combined properdin and mannose-binding lectin deficiency and infection with Neisseria meningitidis.

  2006cited by this paper
• Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

  2002cited by this paper

• Trained Immunity and Its Potential Implications in the Etiopathogenesis of Hidradenitis Suppurativa: A New Paradigm in Chronic Inflammation?

  2025cites this paper
• A Study on the Correlation between Serum Lipid Levels and Disease Activity in Patients with Systemic Lupus Erythematosus

  2025cites this paper
• Management of penoscrotal hidradenitis: a narrative review.

  2025cites this paper
• Advances in Bioprinting to Model Immune-Mediated Skin Diseases.

  2025cites this paper
• Congenital Immunodeficiencies in Infants: Mechanisms, Diagnosis, and Emerging Therapies

  2025cites this paper
• IRAK4 Targeting: A Breakthrough Approach to Combat Hidradenitis Suppurativa

  2025cites this paper
• Hidradenitis suppurativa as a potential risk factor of periodontitis: a multi-center, propensity-score-matched cohort study

  2024cites this paper
• An Atlas of the Hidradenitis Suppurativa Transcriptome

  2024cites this paper
• Immune Dysregulation and Current Targeted Biologics in Hidradenitis Suppurativa

  2024cites this paper
• Cytokine-Mediated Molecular Pathophysiology of Hidradenitis Suppurativa: A Narrative Review

  2024influential citation
• Exploring the Phytochemical Composition and Biological Potential of Balkan Endemic Species Stachys scardica Griseb

  2023cites this paper
• Complement as a vital nexus of the pathobiological connectome for acute respiratory distress syndrome: An emerging therapeutic target

  2023cites this paper
• The complement system as a key modulator of the oral microbiome in health and disease

  2023cites this paper
• Impact of neutrophil extracellular traps on fluid properties, blood flow and complement activation

  2022cites this paper
• Serum Immunoglobulin G Is a Marker of Hidradenitis Suppurativa Disease Severity

  2022cites this paper
• Innate immunity and microbial dysbiosis in hidradenitis suppurativa – vicious cycle of chronic inflammation

  2022cites this paper
• Follicular Occlusion and Inflammation

  2022cites this paper
• The pathogenesis of hidradenitis suppurativa: Evolving paradigms in a complex disease

  2022cites this paper
• Soluble Factors and Receptors Involved in Skin Innate Immunity—What Do We Know So Far?

  2021cites this paper
• Elevated Plasma Complement Proteins in Palmoplantar Pustulosis: A Potential Therapeutic Target

  2021cites this paper
• Target molecules for future hidradenitis suppurativa treatment

  2021cites this paper
• High inflammation in HS extends to perilesional skin, and can be subdivided by LCN2 expression.

  2021cites this paper
• Systemic lupus erythematosus patients have a distinct structural and functional skin microbiota compared with controls

  2021cites this paper
• An outline of SARS-CoV-2 pathogenesis and the complement cascade of immune system

  2021cites this paper
• Clinical Implementation of Biologics and Small Molecules in the Treatment of Hidradenitis Suppurativa

  2021cites this paper
• Hidradenitis suppurativa: A folliculotropic disease of innate immune barrier dysfunction?

  2021cites this paper
• Insights into the Pathogenesis of HS and Therapeutical Approaches

  2021cites this paper
• Primary alterations during the development of hidradenitis suppurativa

  2021cites this paper
• Proceeding report of the fourth Symposium on Hidradenitis Suppurativa Advances (SHSA) 2019.

  2020cites this paper
• Hidradenitis suppurativa is an autoinflammatory keratinization disease: A review of the clinical, histologic, and molecular evidence

  2020cites this paper
• What causes hidradenitis suppurativa ?—15 years after

  2020cites this paper
• Association of Human Leukocyte Antigens Class II Variants with Susceptibility to Hidradenitis Suppurativa in a Caucasian Spanish Population

  2020cites this paper
• A Systematic Review of Promising Therapeutic Targets in Hidradenitis Suppurativa: A Critical Evaluation of Mechanistic and Clinical Relevance.

  2020cites this paper
• Pyoderma gangrenosum: proposed pathogenesis and current use of biologics with an emphasis on complement C5a inhibitor IFX-1

  2020cites this paper
• Ex Vivo Models and Interpretation of Mechanistic Studies in Hidradenitis Suppurativa.

  2020cites this paper