IL-23R in laryngeal cancer: a cancer immunoediting process that facilitates tumor cell proliferation and results in cisplatin resistance.

Oncogenic pathogens can disturb tissue homeostasis and initiate immune responses for oncogenicity clearance and homeostasis restoration, while failed clearance and chronic inflammation may result in tumorigenesis. The primary tumor development will undergo a cancer immunoediting process, including three phases, termed elimination, equilibrium and escape. Importantly, immune-edited tumor cells can not only reduce immunogenic molecular expression but also manipulate cytokines within the tumor environment (TME) for immune evasion and tumor proliferation. Many studies have revealed that IL-23R performed an essential role in mucous inflammation and tumorigenesis, and the role of IL-23R, either in tumor-infiltrating lymphocytes (TILs) or within immune-edited tumor cells, remained largely unknown in laryngeal cancer (LC). Here, we separately analyzed the IL-23R expression in LC TILs and tumor cells and found that high IL-23R expression in tumor cells was associated with moderate and poor tumor differentiation and an unfavorable prognosis. Furthermore, the real-time quantitative polymerase chain reaction analysis revealed that human LC tissues overexpress signal transducers and activators of transcription 3 (STAT3), and the relevance analysis found this STAT3 overexpression had a significant correlation with IL-23R expression. Besides, we isolated and cultured IL-23R+ human tumor cells from the postoperation tumor sample of three LC patients, and found that rhIL-23 could phosphorylate STAT3 (pSTAT3, residue Y705), which resulted in cancer cell proliferation and cisplatin resistance. These results indicate that IL-23R was a Hallmark of cancer immunoediting process, and targeting IL-23 should be considered as a therapeutic option for laryngeal function preservation and survival improvement.

M2 Macrophages Promote Collagen Expression and Synthesis in Laryngotracheal Stenosis Fibroblasts.

OBJECTIVE: Macrophages exhibit distinct phenotypes and are dysregulated in a model of iatrogenic laryngotracheal stenosis (iLTS). Increased populations of alternatively activated or M2 macrophages have been demonstrated. However, the role of these macrophages is unknown. The aims of this study are: 1) define the macrophage population in iLTS in the context of classically activated or M1 and M2 macrophage phenotypes, and 2) characterize the effect of monocyte-derived M1 and M2 macrophages on normal airway and LTS-derived fibroblasts (FBs) in vitro. STUDY DESIGN: Comparative analysis; in vitro controlled study. METHODS: Immunohistochemical analysis of human iLTS and control specimens was performed to define the macrophage population. In vitro, M1, and M2 macrophages were polarized using M-CSF + Interferon-gamma and lipopolysaccharide or Interleukin-4, respectively. FBs isolated from laryngotracheal scar (LTS-FBs) and normal tracheal airway (NA-FBs) in eight patients with iLTS were cocultured with polarized macrophages. Fibrosis gene expression, soluble collagen production, and proliferation were assessed. RESULTS: Immunohistochemical analysis revealed increased CD11b + cells (macrophage marker) in laryngotracheal scar specimens (18.3% vs. 8.5%, P = .03) and predominant CD206 (M2) costaining versus CD86 (M1) (51.5% vs. 9.8%, n = 10, P = .001). In vitro, NA-FBs cultured with M2 macrophages demonstrated a 2.41-fold increase in collagen-1 expression (P = .05, n = 8) and an increase in soluble collagen (9.98 vs. 8.875, mean difference: 1.11 95%, confidence interval 0.024-2.192, n = 8, P = .015). CONCLUSION: Increased populations of CD11b cells are present in iLTS specimens and are predominantly CD206+, indicating an M2 phenotype. In vitro, M2 macrophages promoted collagen expression in airway FBs. Targeting macrophages may represent a therapeutic strategy for attenuating fibrosis in iLTS. LEVEL OF EVIDENCE: NA Laryngoscope, 131:E346-E353, 2021.

T-Helper 2 Lymphocyte Immunophenotype Is Associated With Iatrogenic Laryngotracheal Stenosis.

OBJECTIVE/HYPOTHESIS: This prospective controlled human and murine study assessed the presence of inflammatory cells and cytokines to test the hypothesis that immune cells are associated with fibroproliferation in iatrogenic laryngotracheal stenosis (iLTS). METHODS: Inflammation was assessed by histology and immunofluorescence (IF), quantitative real-time polymerase chain reaction (qRT-PCR), and flow cytometry of cricotracheal resections of iLTS patients compared to normal controls. An iLTS murine model assessed the temporal relationship between inflammation and fibrosis. RESULTS: iLTS specimens showed increased inflammation versus normal controls (159/high power field [hpf] vs. 119/hpf, P = 0.038), and increased CD3 + T-cells, CD4 + cells, and CD3+/CD4 + T-helper (TH ) cells (all P < 0.05). The inflammatory infiltrate was located immediately adjacent to the epithelial surface in the superficial aspect of the thickened lamina propria. Human flow cytometry and qRT-PCR showed a significant increase in interleukin (IL)-4 gene expression, indicating a TH 2 phenotype. Murine IF revealed a dense CD4 + T-cell inflammatory infiltrate on day 4 to 7 postinjury, which preceded the development of fibrosis. Murine flow cytometry and qRT-PCR studies mirrored the human ones, with increased T-helper cells and IL-4 in iLTS versus normal controls. CONCLUSION: CD3/CD4 + T-helper lymphocytes and the proinflammatory cytokine IL-4 are associated with iLTS. The association of a TH 2 immunophenotype with iLTS is consistent with findings in other fibroinflammatory disorders. The murine results reveal that the inflammatory infiltrate precedes the development of fibrosis. However, human iLTS specimens with well-developed fibrosis also contain a marked chronic inflammatory infiltrate, suggesting that the continued release of IL-4 by T-helper lymphocytes may continue to propagate iLTS. LEVEL OF EVIDENCE: NA Laryngoscope, 129:177-186, 2019.

Allergic laryngitis: unraveling the myths.

PURPOSE OF REVIEW: This article provides a thorough review of the literature highlighting the articles that have advanced our knowledge about the sensitivity of the larynx to allergens in the air or ones consumed. This area of inquiry requires continued interest and investigation. As the field of clinical laryngology changes, and more information is discovered about the possible causal association between allergy and vocal pathologies, practicing otolaryngologists, allergists, and other medical professionals may discover more comprehensive methods to evaluate and treat their allergic patients, particularly those who present with complaints of dysphonia, dysphagia, laryngopharyngeal reflux (LPR), and/or dyspnea. RECENT FINDINGS: There continues to be epidemiological studies designed to describe the relationship of allergy to vocal symptoms and signs. Both population and smaller studies have recently attempted to link these two conditions. Unfortunately, the patient with chronic laryngeal complaints is often tagged by default with the diagnosis of LPR and treated with proton pump inhibitors, which are not always beneficial. The endoscopic assessment may not be as reliable to make the diagnosis of LPR as the examination is subjective and the inter-rater reliability is low. It has been demonstrated by direct laryngeal provocation studies that sticky-viscous endo-laryngeal mucous is the only reliable finding consistently associated with allergy potential allergic tissue reactivity. SUMMARY: The interrelationship of allergic sensitivity and chronic laryngitis in certain individuals is becoming clearer because our knowledge of inquiry has increased and the available routine technology to diagnose these conditions has remarkably improved. Notwithstanding these advancements, much more research is needed on this subject to reduce the frequency of mis-diagnoses and mis-management of allergic patients.

Angioedema associated with nonsteroidal anti-inflammatory drugs.

PURPOSE OF REVIEW: The review critically assesses the different phenotypes of angioedemas associated with NSAIDs. Angioedemas exacerbated or induced by NSAIDs have high morbidity and, when they affect the larynx, can lead to death by asphyxiation. RECENT FINDINGS: Angioedema can present as a manifestation of a syndrome such as anaphylaxis or it can be a separate entity, which comprises different forms that can be diagnosed based on specific criteria. NSAIDs are the drugs most used worldwide and they are also one of the leading causes of angioedema. SUMMARY: The manuscript addresses the pathophysiology and pharmacogenetics of angioedema, reviews its classification and assesses the diagnosis and management of angioedemas exacerbated and induced by NSAIDs.

Characteristics of laryngeal symptoms induced in patients with allergic rhinitis in an environmental challenge chamber.

BACKGROUND: People with allergic rhinitis often have laryngeal symptoms (LSs) in addition to nasal symptoms during the pollen-scattering season. OBJECTIVE: To clarify the characteristics of the LSs induced by pollen exposure using an environmental challenge chamber. METHODS: Cypress pollen exposure using an environmental challenge chamber for 25 participants with cypress pollen-induced allergic rhinitis was performed for 3 hours for 2 consecutive days in 3 study courses: namely, pollen exposure under normal nasal breathing and pollen or sham pollen exposure with nasal blockage, which eliminated any allergic reactions in the nasal mucosa. The nasal and LSs scores and the levels of serum inflammatory mediators, including eosinophil cationic protein (ECP), were monitored. Laryngeal examinations and physiologic lung tests were also conducted. RESULTS: Various LSs were reported, and these LSs were significantly elevated during pollen exposure and even under sham exposure with artificial nasal blockage. The pollen exposure with artificial nasal blockage exaggerated the LSs in 32% of the participants and also increased the serum ECP levels. The serum ECP levels did not change after sham exposure. The findings of both laryngeal examinations and lung tests failed to reveal any significant changes. CONCLUSION: Nasal obstruction could induce significant LSs even without pollen exposure. LSs were enhanced by pollen exposure and allergic reactions in the larynx could thus be involved in this enhancement. TRIAL REGISTRATION: clinicaltrials.gov Identifier: UMIN000015667.

Significant laryngeal destruction in a northern European cohort of Behçet's disease patients.

OBJECTIVES: Behçet's disease (BD) is a multisystem autoimmune disease of unknown origin typically affecting the triad of oral and genital mucosa and the eye. Limited data are available in the literature regarding the otolaryngology-related manifestations of BD, particularly in northern Europeans. This is a novel study detailing surprising and significant laryngeal structural changes in a northern European cohort of BD. METHODS: Patients meeting the International Study Group for Behçet's Disease (ISGBD) and the International Criteria for Behçet's Disease (ICBD) criteria for diagnosis were identified from an institutional database. Patients underwent examination with an otolaryngologist, including flexible laryngoscopy. Intra-oral, pharyngeal and laryngeal manifestations of BD were documented and characterised. Patients underwent hearing assessment with pure-tone audiometry. RESULTS: Fifteen patients with BD were identified (4 male, 11 female; median age 36 years). 60% (n=9) showed evidence of disease on examination and flexible laryngoscopy. 33% (n=5) showed laryngeal changes related to BD. 13% (n=2) demonstrated bilateral sensorineural hearing loss. The 5 cases demonstrating laryngeal manifestations of disease are described in detail with photographic records. CONCLUSIONS: Limited data has been published regarding the laryngeal manifestations of BD, particularly in a northern European population. Our cohort of BD patients demonstrate significant laryngeal structural changes. It would appear that these clinically relevant changes may be more common than was previously thought. Raised awareness of the risk of laryngeal pathology in BD patients, often in the absence of overt clinical symptomatology, may result in earlier diagnosis and treatment. Rheumatologists and otolaryngologists should consider closer multi-disciplinary co-operation in the management and follow up of patients with BD.

Retinoic acid-inducible gene-I-like receptor (RLR)-mediated antiviral innate immune responses in the lower respiratory tract: Roles of TRAF3 and TRAF5.

Upon viral infection, the cytoplasmic viral sensor retinoic acid-inducible gene-I (RIG-I) recognizes viral RNA to activate antiviral signaling to induce type I interferon (IFN). RIG-I-like receptors (RLRs) activate antiviral signaling in a tissue-specific manner. The molecular mechanism underlying antiviral signaling in the respiratory system remains unclear. We studied antiviral signaling in the lower respiratory tract (LRT), which is the site of many harmful viral infections. Epithelial cells of the LRT can be roughly divided into two groups: bronchial epithelial cells (BECs) and pulmonary alveolar epithelial cells (AECs). These two cell types exhibit different phenotypes; therefore, we hypothesized that these cells may play different roles in antiviral innate immunity. We found that BECs exhibited higher antiviral activity than AECs. TNF receptor-associated factor 3 (TRAF3) has been shown to be a crucial molecule in RLR signaling. The expression levels of TRAF3 and TRAF5, which have conserved domains that are nearly identical, in the LRT were examined. We found that the bronchus exhibited the highest expression levels of TRAF3 and TRAF5 in the LRT. These findings suggest the importance of the bronchus in antiviral innate immunity in the LRT and indicate that TRAF3 and TRAF5 may contribute to RLR signaling.

[Morphological changes of lymphoid apparatus of the larynx after experimental exposure to various balneal factors].

The aim of this investigation was to detect the structural changes of lymphoid components of rat pharynx in an experiment after a course of exposure to various balneal procedures. The studies were performed on 90 outbred mature 3 month-old male rats (20 animals in each experimental group and 10 animals in each control groups). The animals were exposed to a course of weakly mineralized organic bituminous, thermal iodobromine and strong (concentrated) sulfide baths present on the territory of Azerbaijan. The experiments performed have shown a significant sensitivity of the lymphoid structures of the rat pharynx to the balneal procedures. After exposure to iodobromine and bituminous baths, the signs of lymphocytopoiesis activation were noted. The exposure to strong sulfide baths resulted in a morphological regression of lymphoid apparatus of rat larynx, which raises the question on the expediency of the use of these procedures in practical balneology.

AAOA allergy primer: history and physical examination.

BACKGROUND: Allergic disease is very common in the general population and makes a significant impact on the quality of life of patients. Immunoglobulin E (IgE)-mediated allergic disease manifests throughout the body, but many signs and symptoms of inhalant allergy are centered in the head and neck region. METHODS: A thorough yet focused history of allergic symptoms and potential physical examination findings of inhalant allergy are described. RESULTS: History should include types and timing of symptoms, environmental and occupational exposures, family history, associated diseases, and prior treatment, if any. Physical examination should include the skin and structures of the head and neck region. Nasal endoscopy can be helpful in visualization of nasal polyps. CONCLUSION: Many times, history alone can serve to make the diagnosis, but physical examination also demonstrates specific findings that confirm the practitioner's presumptive diagnosis of allergic disease. However, should medical treatment fail or the diagnosis be in doubt, further diagnostic investigation with allergy testing should be pursued.

Decreased Langerhans cell responses to IL-36γ: altered innate immunity in patients with recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis (RRP) is a rare, chronic disease caused by human papillomaviruses (HPVs) types 6 and 11 that is characterized by the polarization of adaptive immune responses that support persistent HPV infection. Respiratory papillomas express elevated mRNA levels of IL-36γ, a proinflammatory cytokine in comparison to autologous clinically normal laryngeal tissues; however there is no evidence of inflammation in these lesions. Consistent with this, respiratory papillomas do not contain TH1-like CD4(+) T-cells or cytotoxic CD8(+) T-cells, but instead contain a predominance of TH2-like and T regulatory cells (Tregs). In addition, papillomas also are infiltrated with immature Langerhans cells (iLCs). In this study, we show that papilloma cells express IL-36γ protein, and that human keratinocytes transduced with HPV11 have reduced IL-36γ secretion. We now provide the first evidence that peripheral blood-derived iLCs respond to IL-36γ by expressing inflammatory cytokines and chemokines. When stimulated with IL-36γ, iLCs from patients with RRP had lower expression levels of the TH2-like chemokine CCL-20 as compared with controls. Patients' iLCs also had decreased steady state levels of CCL-1, which is a proinflammatory chemokine. Moreover, CCL-1 levels in iLCs inversely correlated with the severity of RRP. The combined decrease of TH1- and a TH2-like chemokines by iLCs from patients could have consequences in the priming of IFN-γ expression by CD8(+) T-cells. Taken together, our results suggest that, in RRP, there is a defect in the proinflammatory innate immune responses made by iLCs in response to IL-36γ. The consequence of this defect may lead to persistent HPV infection by failing to support an effective HPV-specific, TH1-like and/or Tc1-like adaptive response, thus resulting in the predominant TH2-like and/or Treg micromilieu present in papillomas.

[Cycloferon in therapy of hyperplastic laryngitis for decrease of the number of relapses].

The article describes the clinical forms of chronic hyperplastic laryngitis, characterized by persistent and recurrent course, a tendency to the formation of oncological pathology, at the expense of hyperplastic changes in the larynx, leading to a malignancy of the inflammatory process. It was demonstrated the bacterization of larynx by Epstein-Barr virus (EBV) and Mycoplasma in imbalance of system of interferon. Clinical recovery, depending on the clinical form of the disease, using cycloferon, was observed in 57.4% of patients. The inclusion in the complex of the medical support of chronic hyperplastic laryngitis inducer of interferon - cycloferon, provided the reduction of the number of relapses.

Evidence for primary laryngeal inhalant allergy: a randomized, double-blinded crossover study.

BACKGROUND: Despite anecdotal reports, no controlled studies to date link allergen exposure with a change in vocal function or dysphonia. The aim of this study was to determine whether allergen exposure in susceptible individuals impairs vocal function. METHODS: The study was a prospective, double-blind, placebo-controlled study in which subjects serve as their own controls. The participants were 5 inhalant allergic adults with suspected dysphonia from allergies, without evidence of reactive lower airways based on methacholine challenge. All subjects were exposed to 2 experimental conditions in which they were challenged with (1) orally inhaled diluent placebo on 1 day, and (2) orally inhaled allergen on another day. Conditions were randomly ordered across subjects and separated by at least 48 hours. Phonatory threshold pressure (PTP) at the 80th percentile pitch was measured prior to diluent and allergen challenge, and 15 and 60 minutes postchallenge to assess potential change in vocal function after challenge testing. RESULTS: A repeated measures ANOVA revealed a significant main effect for treatment (allergen vs placebo, p = 0.013) with greater PTP required post-allergen challenge compared to placebo and an effect size of 0.821. CONCLUSION: A primary causal relationship between allergen exposure and impaired vocal function, as assessed by PTP, was observed in adults with documented allergy independent of asthma or nasal exposure. The current design establishes a safe model for laryngeal inhalant allergen challenge.

[Cycloferon in complex therapy management of chronic laryngitis].

The clinical course of various forms of chronic laryngitis, including contact granulomas not only persistant and relapsing, but also inclined to oncologic pathology due to hyperplastic changes in the larynx resulting in malignization was described. Inhibition of the leukocyte interferon-synthesizing activity was observed in more than 88.1% of the subjects. Pathogenic viruses were isolated from 48.2% of the patients, EBV and mycoplasma prevailing. High direct correlation between chronic laryngitis and Herpes viruses was shown. The presence of three-component virus associations in the larynx mucosa was likely indicative of the bening process malignancy. The use of the interferon inductor cycloferon in the complex surgical and medicamentous management of chronic laryngitis was shown valid. The rate of the relapses lowered to 1.7 episodes a year.

Nanostructured calcium silicate hydrate seeds accelerate concrete hardening: a combined assessment of benefits and risks.

Nanotechnology creates new possibilities to control and improve material properties for civil infrastructure. Special focus in this area is put on Portland cement and gypsum. Together their annual production is by far larger than for any other material worldwide. Nanomodification of these materials can be done during the few hours between dissolution and hardening, especially by nucleation of the re-crystallization with suitable colloids. Here we report first results in homogeneous seeding of the precipitation of calcium silicate hydrates within a real Portland cement composition. The occupational safety during the production phase and during mixing of concrete paste is addressed in detail by in vivo testing. We perform 5-day inhalation with 21-day recovery in rats and analyze organ-specific toxicity and 71 endpoints from bronchoalveolar lavage (BALF) and blood. In BALF parameters, no test-related changes were observed, indicating the generally low toxicity of the test material. Some mild lesions were observed in larynx level. In the lungs, all animals of the 50 mg/m³ concentration group revealed a minimal to mild increase in alveolar macrophages, which recovered back to control level.

Laryngeal transplantation in minipigs: early immunological outcomes.

Despite recent tissue-engineering advances, there is no effective way of replacing all the functions of the larynx in those requiring laryngectomy. A recent clinical transplant was a success. Using quantitative immunofluorescence targeted at immunologically relevant molecules, we have studied the early (48 h and 1 week) immunological responses within larynxes transplantated between seven pairs of National Institutes of Health (NIH) minipigs fully homozygous at the major histocompatibility complex (MHC) locus. There were only small changes in expression of some molecules (relative to interindividual variation) and these were clearest in samples from the subglottic region, where the areas of co-expression of CD25(+) CD45RC(-) CD8(-) and of CD163(+) CD172(+) MHC-II(-) increased at 1 week after transplant. In one case, infiltration by recipient T cells was analysed by T cell receptor (TCR) Vß spectratype analysis; this suggested that changes in the T cell repertoire occur in the donor subglottis mucosal tissues from day 0 to day 7, but that the donor and recipient mucosal Vß repertoires remain distinct. The observed lack of strong immunological responses to the trauma of surgery and ischaemia provides encouraging evidence to support clinical trials of laryngeal transplantation, and a basis on which to interpret future studies involving mismatches.

Evidence of the local immune status in the human larynx.

We have studied the presence of local immunity in the larynx and its role and development of laryngeal glands in the human larynx. The local immune status in laryngeal secretion or related tissue specimens from the laryngeal ventricle was examined and the results were analyzed between individuals with or without head and neck cancer. Laryngeal secretions or mucosal tissue specimens were obtained during the microscopic laryngeal surgery or at the time of the surgery of the larynx. The laryngeal secretion contained immunological factors such as IgG, IgM, IgA or secretory IgA (SIgA). The mean level of SIgA of the mucosal tissue was low in patients with the benign laryngeal disease and considerably decreased in patients with previous radiation therapy. The level of SIgA in the laryngeal secretion closely correlated to the level of SIgA in the mucosal tissue. From the present study, we confirmed the actual presence of local immune function in the human larynx. Furthermore, the local immune status is affected by either the presence of malignancy or the treatment to the larynx such as radiation.

[Lymphatic tissue of the nose (NALT) and larynx (LALT) in species comparison: human, rat, mouse]. / Das lymphatische Gewebe der Nase (NALT) und des Kehlkopfes (LALT) im Speziesvergleich: Mensch, Ratte, Maus.

Nose- and larynx associated lymphatic tissues (NALT and LALT) vary markedly between humans, rats and mice. NALT of rats and mice is formed by paired lymphoid aggregates in the nasal cavity, while it consists of individual mucosa associated lymphoid follicles throughout the nose in humans. In addition to NALT, tonsils are present in humans, but not in rats and mice. In the larynx, LALT can be found in humans, but not in rats. Size and functionality of NALT, tonsils and LALT vary with age. The extrapolation of data obtained from rodents to humans should be carefully evaluated due to these differences. The term common mucosal immune system should replaced by the term "integrated" MALT and the immunological differences between respiratory and digestive tract should always be considered.

Immunological responses against human papilloma virus and human papilloma virus induced laryngeal cancer.

OBJECTIVE: This study aimed to clarify the local immune status in the larynx in the presence of infection or carcinogenesis associated with human papilloma virus. METHODS: Cytological samples (for human papilloma virus detection) and laryngeal secretions (for immunoglobulin assessment) were obtained from 31 patients with laryngeal disease, during microscopic laryngeal surgery. On histological examination, 12 patients had squamous cell carcinoma, four had laryngeal papilloma and 15 had other benign laryngeal disease. Cytological samples were tested for human papilloma virus DNA using the Hybrid Capture 2 assay. RESULTS: High risk human papilloma virus DNA was detected in 25 per cent of patients (three of 12) with laryngeal cancer. Low risk human papilloma virus DNA was detected only in three laryngeal papilloma patients. The mean laryngeal secretion concentrations of immunoglobulins M, G and A and secretory immunoglobulin A in human papilloma virus DNA positive patients were more than twice those in human papilloma virus DNA negative patients. A statistically significant difference was observed between the secretory immunoglobulin A concentrations in the two groups. Patients with laryngeal cancer had higher laryngeal secretion concentrations of each immunoglobulin type, compared with patients with benign laryngeal disease. The study assessed the mean laryngeal secretion concentrations of each immunoglobulin type in the 12 laryngeal cancer patients, comparing human papilloma virus DNA positive patients (n = 3) and human papilloma virus DNA negative patients (n = 9); the mean concentrations of immunoglobulins M, G and A and secretory immunoglobulin A tended to be greater in human papilloma virus DNA positive cancer patients, compared with human papilloma virus DNA negative cancer patients. CONCLUSION: These results suggest that the local laryngeal immune response is activated by infection or carcinogenesis due to human papilloma virus. The findings strongly suggest that secretory IgA has inhibitory activity against infection or carcinogenesis associated with human papilloma virus in the larynx.

Histopathology of anti-laminin 5 mucous membrane pemphigoid.

BACKGROUND: Anti-laminin 5 mucous membrane pemphigoid (MMP) is an autoimmune blistering disease characterized by autoantibodies against the major basement membrane component laminin 5 (laminin 332, epiligrin). OBJECTIVE AND METHODS: We reviewed 17 biopsy specimens from 9 patients with anti-laminin 5 MMP in an attempt to define typical histopathologic features of the disease. RESULTS: Fifteen specimens showed subepidermal blister formation, while two biopsy specimens revealed an epithelial ulcer. In 11 biopsies a sparse to moderate inflammatory infiltrate composed of lymphocytes and neutrophils with some eosinophils was observed. Four biopsies showed a dense infiltrate dominated by neutrophils in two cases and by eosinophils in one case. The remaining biopsy revealed a dense lymphoplasmacellular infiltrate without granulocytes. Scarring of the upper dermis was present only in 5 specimens. Immunohistochemical analysis localized type IV collagen to the dermal side of the blister, suggesting that split formation occurred within the lamina lucida of the cutaneous basement membrane. LIMITATIONS: The number of patients studied was relatively small. CONCLUSIONS: Histopathology of anti-laminin 5 MMP is characterized by subepidermal blistering and a sparse to moderate superficial lymphohistiocytic infiltrate with neutrophils and/or eosinophils. Both infiltrate density and composition may vary, making anti-laminin 5 MMP indistinguishable from other autoimmune subepidermal blistering diseases by histopathology alone. Scarring is present only in a minority of cases and is not a sensitive clue to the diagnosis of anti-laminin 5 MMP.