Search Results (924)

This study examined the distribution and disease associations of non-HLA-B*27 HLA-B alleles in Romanian spondyloarthritis (SpA) patients, aiming to address the underrepresentation of Eastern European populations in immunogenetic research. Methods: We analyzed 263 HLA-B*27-negative patients from Northeastern Romania fulfilling ASAS criteria. HLA-B genotyping was performed at two-digit resolution, and allele distributions were compared with two Romanian HLA-B*27-negative control groups (n = 335 and n = 1705 cases), using chi-square testing and logistic regression. Compared to controls, HLA-B*47 (p = 0.0007) and HLA-B*54 (p = 0.0013) were significantly enriched, while HLA-B*40 was underrepresented (p = 0.0287). Notably, HLA-B*54 was observed exclusively in axial SpA. Within the cohort, both HLA-B*13 and HLA-B*57 alleles were associated with psoriasis, while HLA-B*37 and HLA-B*41 alleles were clustered within the reactive arthritis group. The HLA-B*35 and HLA-B*18 alleles were the most frequently observed alleles across most clinical phenotypes. When comparing the frequency of HLA-B associations, the most common genotypes among SpA patients were B*08-B*18, B*13-B*35, and B*35-B*51. Notably, B*08-B*18 was more frequent in patients with radiographic sacroiliitis grade ≥ 2, while B*35-B*51 was more frequent in those with confirmed systemic inflammation, as indicated by elevated CRP or ESR levels. Analysis of peptide-binding patterns revealed a cluster of risk alleles, HLA-B*08, B*18, B*35, B*40, and B*54, sharing similar features, distinct from the canonical profile of B*27. These findings highlight the contribution of non-B*27 HLA-B alleles to SpA susceptibility in an Eastern European population and support the notion that HLA-B*27-negative SpA may represent a distinct clinical and immunological entity, driven by alternative pathogenic mechanisms. They also emphasize the importance of population-specific immunogenetic profiling and support expanding genetic characterization in HLA-B*27-negative patients. Full article

Allergic contact dermatitis (ACD) is an immunologic reaction to a dermal chemical exposure that, once triggered in an individual, will result in an allergic response following subsequent encounters with the allergen. Air Force epidemiological consultations have indicated that aircraft structural maintenance workers may experience ACD at elevated rates compared to other occupations. We aimed to better understand the utility of non-animal testing methods in characterizing the sensitization potential of chemicals used during Air Force operations by evaluating the skin sensitization hazard of Air Force-relevant chemicals using new approach methodologies (NAMs) in a case study. We also evaluated the use of NAM data to develop preliminary candidate surface guidelines (PCSGs, maximum concentrations of chemicals on workplace surfaces to prevent induction of dermal sensitization) for chemicals identified as sensitizers. NAMs for assessing skin sensitization, including in silico models and experimental assays, were leveraged into an integrated approach to predict sensitization hazard for 19 chemicals. Local lymph node assay effective concentration values were predicted from NAM assay data via previously published quantitative models. The derived values were used to calculate PCSGs, which can be used to compare the presence of these chemicals on work surfaces to better understand the risk of Airmen developing ACD from occupational exposures. Full article

Cystic echinococcosis is a zoonosis caused by the cestode Echinococcus granulosus sensu stricto. Population genetic studies and phylogeographic patterns are essential to understanding the transmission dynamics of this parasite under varying environmental conditions. In this study, the genetic diversity of E. granulosus s.s. was evaluated using 46 hydatid cyst samples obtained from sheep, goats, cattle, and humans across three regions of Chile: Coquimbo, La Araucanía, and Magallanes. Mitochondrial cox1 gene sequences were analyzed and compared with reference sequences reported from South America, Europe, Africa, Asia, and Oceania. In Chile, the EG01 haplotype was the predominant haplotype. A total of four haplotypes were identified, with low haplotype diversity (Hd = 0.461 ± 0.00637) and low nucleotide diversity (π = 0.00181 ± 0.00036). The haplotype network displayed a star-like configuration, with the EG01 genotype at the center, suggesting a potentially ancestral or widely distributed lineage. In Coquimbo (Tajima’s D = −0.93302, p = 0.061; Fu’s Fs = −0.003, p = 0.502) and Magallanes (Tajima’s D = −0.17406, p = 0.386; Fu’s Fs = −0.121, p = 0.414), both neutrality tests were non-significant, indicating no strong evidence for recent population expansion or selection. Star-like haplotype network patterns were also observed in populations from Europe, the Middle East, Asia, Africa, and Oceania, with the EG01 genotype occupying the central position. The population genetic structure of Echinococcus granulosus s.s. in Chile demonstrates considerable complexity, with EG01 as the predominant haplotype. Further comprehensive studies are required to assess the intraspecific genetic variability of E. granulosus s.s. throughout Chile and to determine whether this variability influences the key biological traits of the parasite. This structure may prove even more complex when longer fragments are analyzed, which could allow for the detection of finer-scale microdiversity among isolates from different hosts. We recommended that future cystic echinococcosis control programs take into account the genetic variability of E. granulosus s.s. strains circulating in each endemic region, to better understand their epidemiological, immunological, and possibly pathological differences. Full article

Background: Angiosarcomas (ASs) represent a heterogeneous and highly aggressive subset of tumors that respond poorly to systemic treatments and are associated with short progression-free survival (PFS) and overall survival (OS). The aim of this study was to develop and validate an immune-related prognostic model—termed the AS score—using data from two independent sarcoma cohorts. Methods: A prognostic model was developed using a previously characterized cohort of 25 angiosarcoma samples. Candidate genes were identified via the Maxstat algorithm (Maxstat v0.7-25 for R), combined with log-rank testing. The AS score was then computed by weighing normalized gene expression levels according to Cox regression coefficients. For external validation, transcriptomic data from TCGA Sarcoma cohort (n = 253) were analyzed. The Immunoscore—which reflects the tumor immune microenvironment—was inferred using the ESTIMATE package (v1.0.13) in R. All statistical analyses were performed in RStudio (v 4.0.3). Results: Four genes—IGF1R, MAP2K1, SERPINE1, and TCF12—were ultimately selected to construct the prognostic model. The resulting AS score enabled the classification of angiosarcoma cases into two prognostically distinct groups (p = 0.00012). Cases with high AS score values, which included both cutaneous and non-cutaneous forms, exhibited significantly poorer outcomes, whereas cases with low AS scores were predominantly cutaneous. A significant association was observed between the AS score and the Immunoscore (p = 0.025), with higher Immunoscore values found in high-AS score tumors. Validation using TCGA sarcoma cohort confirmed the prognostic value of both the AS score (p = 0.0066) and the Immunoscore (p = 0.0029), with a strong correlation between their continuous values (p = 2.9 × 10⁻⁸). Further survival analysis, integrating categorized scores into four groups, demonstrated robust prognostic significance (p = 0.00021). Notably, in tumors with a low Immunoscore, AS score stratification was not prognostic. In contrast, among cases with a high Immunoscore, the AS score effectively distinguished outcomes (p < 0.0001), identifying a subgroup with poor prognosis but potential sensitivity to immunotherapy. Conclusions: This combined classification using the AS score and Immunoscore has prognostic relevance in sarcoma, suggesting that angiosarcomas with an immunologically active microenvironment (high Immunoscore) and poor prognosis (high AS score) may be prime candidates for immunotherapy and this approach warrants prospective validation. Full article

Crohn’s disease is a chronic inflammation affecting the gastrointestinal tract. To date, patients are commonly treated with corticosteroids or more aggressive biologics for high-risk subjects. Stem Cell Educator therapy has been successfully utilized to treat patients with type 1 diabetes and other autoimmune conditions. A 78-year-old patient with long-standing Crohn’s disease received one treatment with the Stem Cell Educator therapy, followed by clinical, radiographic, pathological examinations and immune marker testing by flow cytometry. After the treatment with Stem Cell Educator therapy, the patient’s clinical symptoms were quickly improved with normal bowel movements, without abdominal pain or rectal bleeding. Flow cytometry analysis revealed a marked decline in inflammatory markers, such as the percentage of monocyte/macrophage-associated cytokine interleukin-1 beta (IL-1β)⁺ cells, which reduced from 94.98% at the baseline to 18.21%, and down-regulation of the percentage of chemokine CXCL16⁺ cells from 91.92% at baseline to 42.58% at 2-month follow-up. Pathologic examination of the biopsy specimens from colonoscopy five weeks and six months post-treatment showed ileal mucosa with no specific abnormality and no significant inflammation or villous atrophy; no granulomas were identified. A follow-up CT scan four and one-half months post-treatment showed no evidence of the previously seen stenosis of the ilio-colonic anastomosis with proximal dilatation. Stem Cell Educator therapy markedly reduced inflammation in the subject with Crohn’s disease, leading to durable clinical, immunological, radiographic, and pathological improvements. Full article

Chronic inflammatory response syndrome (CIRS) and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) are debilitating multisystem illnesses that share overlapping symptoms and molecular patterns, including immune dysregulation, mitochondrial impairment, and vascular dysfunction. This review provides a chronological synthesis of biomarker development in CIRS, tracing its evolution from early functional tests such as visual contrast sensitivity (VCS) to advanced transcriptomic profiling. Drawing on peer-reviewed studies spanning two decades, we examine the layered integration of neuroendocrine, immunologic, metabolic, and genomic markers that collectively support a multisystem model of innate immune activation specific to environmentally acquired illness. Particular focus is given to the Gene Expression: Inflammation Explained (GENIE) platform’s use of transcriptomics to classify disease stages and distinguish CIRS from other fatiguing conditions. While ME/CFS research continues to explore overlapping pathophysiologic features, it has yet to establish a unified diagnostic model with validated biomarkers or exposure-linked mechanisms. As a result, many patients labeled with ME/CFS may, in fact, represent unrecognized CIRS cases. This review underscores the importance of structured biomarker timelines in improving differential diagnosis and guiding treatment in complex chronic illness and highlights the reproducibility of the CIRS framework in contrast to the diagnostic ambiguity surrounding ME/CFS. Full article

Background: Several epidemiological studies have indicated that metabolic syndrome (MetS) after renal transplantation is caused by an accumulation of non-immunological risks of renal transplantation, and affects the prognosis of the kidney and the patient by increasing the risk of arteriosclerosis and cardiovascular complications. The incidence of MetS in Japanese renal transplant recipients is 14.9 to 23.8%, but its effects on cardiovascular events and kidney prognosis are not clear. Here, we report the results of a longitudinal study on MetS in renal transplant recipients. Methods: A retrospective cohort study was conducted in 104 stable renal transplant recipients who attended our outpatient department from January 2006 to June 2007 and were diagnosed with MetS at least 6 months after renal transplantation until 31 December 2020, or did not have MetS. The impact of MetS on composite vascular events was examined using multivariate Cox proportional hazards analysis. Results: The hazard ratios for the impact of MetS on composite vascular events diagnosed by NCEP Japan, NCEP Original, NCEP Asia, and IDF criteria on composite vascular events were 2.78 (95% CI: 1.15 to 6.75, p = 0.024), 2.65 (95% CI: 1.04 to 6.80, p = 0.042), 2.37 (95% CI: 0.93 to 6.01, p = 0.070), and 1.91 (95% CI: 0.77 to 4.75, p = 0.164), respectively. P for interaction was used to test the influence of each indicator, but was not statistically significant. Conclusions: MetS is a robust risk factor for graft loss and development of cardiovascular events in Japanese renal transplant recipients, even during long-term follow-up. This finding emphasizes the importance of monitoring and managing MetS in this population to improve long-term outcomes. Full article

Background: Pancreas and pancreas–kidney transplantation are well-established therapeutic options for patients with type 1 diabetes mellitus (T1DM) and end-stage kidney disease (ESKD), offering the potential to restore endogenous insulin production and kidney function. It improves metabolic control, quality of life, and long-term survival. While surgical techniques and immunosuppressive strategies have advanced considerably, graft rejection and limited long-term graft survival remain significant clinical challenges. Method: To better understand these risks, the genetic and immunological factors that influence transplant outcomes are examined. Beyond traditional human leukocyte antigen (HLA) matching, non-HLA genetic variants such as gene deletions and single-nucleotide polymorphisms (SNPs) have emerged as contributors to alloimmune activation and graft failure. Result: Polymorphisms in cytokine genes, minor histocompatibility antigens, and immune-regulatory pathways have been implicated in transplant outcomes. However, the integration of such genomic data into clinical practice remains limited due to underexplored gene targets, variability in study results, and the lack of large, diverse, and well-characterized patient cohorts. Initiatives like the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) are addressing these limitations by aggregating genome-wide data from thousands of transplant donors and recipients across multiple centers. These large-scale collaborative efforts aim to identify clinically actionable genetic markers and support the development of personalized immunosuppressive strategies. Conclusions: Overall, genetic testing and genomics hold great promise in advancing precision medicine in pancreas and pancreas–kidney transplantation. Full article

Although platelets have been traditionally thought of to be essential hemostasis mediators, new research shows how important they are for controlling cellular oxidative stress, inflammatory processes, and immunological responses—particularly during major surgery on the abdomen. Perioperative problems are largely caused by the continually changing interaction of inflammatory cytokines, the formation of reactive oxygen species (ROS), and platelet activation. The purpose of this review is to summarize the most recent data regarding the complex function of platelets in abdominal surgery, with an emphasis on how they interact with inflammation and oxidative stress, and to investigate the impact on postoperative therapy and subsequent studies. Recent study data on platelet biology, redox signals, surgical stress, and antiplatelet tactics was reviewed in a systematic manner. Novel tailored therapies, perioperative antiplatelet medication, oxidative biomarkers of interest, and platelet-derived microscopic particles are important themes. In surgical procedures, oxidative stress dramatically increases the reactive capacity of platelets, spurring thromboinflammatory processes that affect cardiac attacks, infection risk, and recovery. A number of biomarkers, including soluble CD40L, thromboxane B2, and sNOX2-derived peptide, showed potential in forecasting results and tailored treatment. Antiplatelet medications are still essential for controlling risk factors for cardiovascular disease, yet using them during surgery necessitates carefully weighing the risks of thrombosis and bleeding. Biomarker-guided therapies, antioxidant adjuncts, and specific platelet inhibitors are examples of evolving tactics. In abdominal procedures, platelets strategically operate at the nexus of oxidative stress, inflammatory processes, and clotting. Improved patient classification, fewer problems, and the creation of individualized surgical care strategies could result from an increased incorporation of platelet-focused tests and therapies into perioperative processes. To improve clinical recommendations, subsequent studies may want to focus on randomized studies, biomarker verification, and using translational approaches. Full article

Background: Kidney transplant recipients (KTRs) exhibit a significantly diminished immune response to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) vaccines compared with the general population, primarily due to ongoing immunosuppressive therapy. This study evaluated the immunogenicity of a third SARS-CoV-2 mRNA vaccine dose in KTRs and assessed the association between antibody response and protection against SARS-CoV-2 breakthrough infection. Additionally, the clinical and immunological correlates of post-vaccination SARS-CoV-2 infection were examined. Methods: A prospective cohort of 135 KTRs received a third vaccine dose approximately six months following the second dose. Plasma samples were collected at baseline (pre-vaccination), six months after the second dose, and six weeks following the third dose. Humoral responses were assessed using SARS-CoV-2-specific Immunoglobulin G (IgG) titers and virus neutralization assays against wild-type (WT) and viral strains, including multiple Omicron sub-lineages. Results: After the third vaccine dose, 74% of the KTRs had detectable SARS-CoV-2-specific IgG antibodies, compared with 48% following the second dose. The mean IgG titers increased approximately ten-fold post-booster. Despite this increase, neutralizing activity against the Omicron variants remained significantly lower than that against the WT strain. KTRs who subsequently experienced a SARS-CoV-2 breakthrough infection demonstrated reduced neutralizing antibody activity across all variants tested. Additionally, individuals receiving triple immunosuppressive therapy had a significantly higher risk of SARS-CoV-2 breakthrough infection compared with those on dual or monotherapy. A multivariate machine learning analysis identified age and neutralizing activity against WT, Delta, and Omicron BA.2 as the most robust correlates of SARS-CoV-2 breakthrough infection. Conclusions: A third SARS-CoV-2 mRNA vaccine dose significantly improves SARS-CoV-2-specific IgG levels in KTRs; however, the neutralizing response against Omicron variants remains suboptimal. Diminished neutralizing capacity and intensified immunosuppression are key determinants of SARS-CoV-2 breakthrough infection in this immunocompromised population. Full article

Background/Objectives: Elevated troponin levels are widely recognized as key biomarkers of myocardial injury and are frequently used in clinical decision making. However, not all instances of troponin elevation indicate true cardiac damage. In some cases, biochemical or immunological interferences may lead to false-positive results. These situations may lead to unnecessary diagnostic interventions and clinical uncertainty, ultimately impacting patient management negatively. This study aims to investigate the underlying mechanisms of false-positive troponin elevation in pediatric patients, focusing on factors such as macrotroponin formation, autoantibodies, and heterophile antibody interference. Methods: This retrospective study analyzed data from 13 pediatric patients who presented with elevated cardiac troponin levels between 2017 and 2024. Clinical evaluations included transthoracic echocardiography (TTE), electrocardiography (ECG), coronary computed tomography angiography (CTA), cardiac magnetic resonance imaging (MRI), and rheumatologic testing. Laboratory findings included measurements of cardiac troponins (cTnI and hs-cTnT) and pro-BNP levels. Results: Among 70 patients evaluated for elevated troponin levels, 13 (18.6%) were determined to have no identifiable cardiac etiology. The median age of these 13 patients was 13.0 years (range: 9–16), with 53.8% being female. The most common presenting complaints were chest pain (53.8%) and palpitations (30.8%). TTE findings were normal in 61.5% of the patients, and all patients had normal coronary CTA and cardiac MRI findings. Although initial troponin I levels were elevated in all cases, persistent positivity was observed up to 12 months. Median cTnI levels were 1.00 ng/mL (range: 0.33–7.19) at week 1 and 0.731 ng/mL (range: 0.175–4.56) at month 12. PEG precipitation testing identified macrotroponin in three patients (23.1%). No etiological explanation could be identified in 10 cases (76.9%), which were considered idiopathic. All patients had negative results for heterophile antibody and rheumatologic tests. Conclusions: When interpreting elevated troponin levels in children, biochemical interferences—especially macrotroponin—should not be overlooked. This study emphasizes the diagnostic uncertainty associated with non-cardiac troponin elevation. To better guide clinical practice and clarify false positivity rates, larger, multicenter prospective studies are needed. Full article

The oral epithelium is essential for maintaining oral health and plays a key role in the onset and progression of periodontitis. It serves as both a mechanical and immunological barrier and possesses antimicrobial activity. Vitamin D₃, a hormone with known immunomodulatory functions, may influence oral epithelial responses. This study investigated the effects of two vitamin D₃ metabolites on key immunological and antimicrobial functions of oral epithelial cells, both under basal conditions and during bacterial challenge. Ca9-22 oral epithelial cells were treated with 1,25(OH)₂D₃ or 25(OH)D₃ in the presence or absence of Tannerella forsythia, Fusobacterium nucleatum, or Porphyromonas gingivalis. Inflammatory responses were assessed by measuring gene and protein expression of IL-1β and IL-8. Antimicrobial activity was evaluated via expression of LL-37, hBD-2, and hBD-3, as well as direct bacterial killing assays. Expression of epithelial integrity markers E-cadherin and ICAM-1 was also analyzed. Vitamin D₃ metabolites reduced IL-8 expression and significantly increased LL-37 expression and production in Ca9-22 cells. Both forms enhanced antimicrobial activity against all tested pathogens and modulated epithelial integrity markers. Vitamin D₃ positively regulates antimicrobial and barrier functions in oral epithelial cells, suggesting a potential role in supporting oral health and preventing periodontitis progression. Full article

Background/Objectives: This study was conducted to analyze the associations between vascular endothelial growth factor (VEGF) serum concentrations and immunological biomarkers, inflammatory parameters, classical atherosclerosis risk factors, and cardiovascular manifestations in systemic lupus erythematosus (SLE) patients. Methods: The project included 83 individuals suffering from SLE, with 20 healthy individuals as controls. The serum levels of VEGF were determined through the ELISA method using R&D Systems tests. Laboratory markers, autoantibody profiles, traditional atherosclerotic risk factors, and organ manifestations were evaluated. Atherosclerotic changes were determined based on several indices including carotid intima-media thickness, ankle-brachial index and high resistance index assessments. Results: The reference range of serum VEGF concentrations was established based on the 25th and 75th percentiles obtained in the controls. High VEGF levels were significantly correlated with the presence of selected anti-phospholipid antibodies such as anti-prothrombin (OR = 10.7; 95%CI: 2.1–53.4) and anti-beta2 glycoprotein I (OR = 3.5; 95%CI: 1.1–10.8), as well as cardiac disorders (OR = 8.0; 95%CI: 1.6–39.5). On the other hand, low concentrations of VEGF were significantly related to lower frequencies of anti-double-stranded DNA antibodies (OR = 0.31; 95%CI: 0.11–0.91) and anti-endothelial cell antibodies (OR = 0.30; 95%CI: 0.11–0.85). Patients with low VEGF levels showed significantly reduced risks of atherosclerotic lesions (OR = 0.24; 95%CI: 0.04–0.99) and vasculitis development (OR = 0.17; 95%CI = 0.03–0.91). Conclusions: In conclusion, VEGF’s pathogenetic role in SLE and SLE-related atherothrombosis is manifested in close correlation with aPLs which may enhance their direct impact on endothelium. High VEGF levels are helpful for identifying cardiovascular risk in patients, while low concentrations indicate lower disease activity, as well as a lower risk of organ involvement. Full article

Non-remitting neutropenia in children and chronic idiopathic neutropenia (CIN) in adults have been described previously as peculiar subgroups of neutropenic patients carrying similar clinical and immunological features. The present collection comprising 25 subjects (16 adults and 9 children) mostly affected with mild (84%) and moderate (16%) neutropenia aimed to identify the underlying (possibly common) genetic background. The phenotype of these patients resemble the one described previously: no severe infections, presence of rheumathological signs, leukopenia in almost all patients and lymphocytopenia in one-third of the cohort. The pediatric patients did not share common genes with the adults, based on the results of the multisample test, while some singular variants in neutropenia potentially associated with immune dysregulation likely consistent with the phenotype were found. SPINK5, RELA and CARD11 were retrieved and seem to be consistent with the clinical picture characterized by neutropenia associated to immune dysregulation. The enrichment and burden tests performed in comparison with a control group underline that the products of expression by the variants involved belong to the autoimmunity and immune regulation pathways (i.e., SPINK5, PTPN22 and PSMB9). Even with the limitation of this study’s low number of patients, these results may suggest that non-remitting neutropenia and CIN in adults deserve deep genetic study and enlarged consideration in comparison with classical neutropenia. Full article

Introduction: Unilateral cleft lip and palate (CLP) is a severe orofacial birth defect characterized by improper fusion of facial parts and disturbed orofacial functions. The defect manifests as a gap in the orofacial tissues that is accompanied by defective healing patterns and chronic inflammation. The immune system’s defense factors modulate immunity, inflammation, and healing. Angiogenesis factors control blood-vessel formation. Therefore, these factors are vital in the immunological assessment and understanding of CLP morphopathogenesis. The aim of the study is to assess the distribution of vascular endothelial growth factor (VEGF), transforming growth factor beta 1 (TGF- β1), the total macrophage population and the M2 subtype, heat-shock proteins (HSP) 60 and 70, and nuclear factor kappa B (NF-κB) p50 and p65 subtypes in the affected tissue of children with CLP before and during primary dentition. Materials and Methods: Tissue samples were obtained from 15 patients aged from 3 to 8 months during veloplastic surgery. Five controls were used for comparison of data. Immunohistochemistry, light microscopy, semi-quantitative evaluation (from 0 to ++++), and statistics (Mann–Whitney U test and Spearman’s rank correlation) were used to evaluate the data for statistically significant differences and correlations between the groups. Results: Epithelial tissues affected by CLP presented with statistically significant increases in levels of VEGF (p = 0.007), total macrophages (p = 0.007), HSP60 (p = 0.001), NF-κB p65 (p = 0.000), and p50 (p = 0.045), but with a decrease in M2 macrophages (p = 0.025). Blood vessels in CLP-affected tissues showed a statistically significant increase in levels of NF-κB p65 (p = 0.003) and a statistically significant decrease in M2 numbers (p = 0.014). Connective tissue presented with no statistically significant differences. Spearman’s rank correlation revealed multiple statistically significant correlations—26 positive and 5 negative. Conclusions: Statistically significant changes in levels of VEGF and both NF-κB subtypes and numbers of total macrophages and M2 macrophages suggest a possible alteration of variable immune and inflammatory reactions and macrophage functions associated with the initiation and maintenance of the chronic process and the resulting damage. Full article