anti-PTX3 Antibodies Research Articles

Anti-pentraxin 3 antibodies and residual disease activity in rheumatoid arthritis.

This study quantified anti-PTX3 antibodies in the serum of seropositive and seronegative rheumatoid arthritis (RA) patients, examining their associations with disease activity and patient-reported outcomes (PROMs). In this cross-sectional study, RA patients diagnosed per ACR/EULAR 2010 criteria were recruited. Seronegative RA was defined as ACPA < 7 kU/l. Data on demographics, clinical characteristics, medications, and PROMs were collected. Serum anti-PTX3 antibodies were measured using an in-house ELISA method. Comparative analyses were conducted with historical controls having psoriatic arthritis (PsA) and fibromyalgia (FM). The cohort included 83 RA patients (42 seropositive, 41 seronegative). Seropositive patients had lower anti-PTX3 antibody levels than PsA (p= 0.001) and FM (p= 0.004) controls. Seronegative patients had higher levels than seropositive ones (p= 0.032). Anti-PTX3 antibodies correlated with CDAI (r = 0.255), PtGA (r = 0.257), VAS-GH (r=-0.235), VAS-pain (r = 0.233), and HAQ (r = 0.311), but not with joint counts, inflammatory markers, or physician's global assessment. The PtGA association remained significant when adjusted for BMI, SJC28, ESR, and prednisone dosage (β = 0.206, p= 0.042). Patients with near-controlled RA (SJC28 ≤ 2, PtGA > 2) had higher anti-PTX3 levels than those with controlled disease (SJC28 ≤ 2, PtGA ≤ 2; p= 0.048). Tocilizumab or abatacept-treated patients had lower levels compared with those on TNFi or JAKi. Elevated anti-PTX3 antibodies in RA indicate residual active disease despite controlled inflammation. They may serve as a biomarker for true active disease, especially in seronegative RA patients who might be undertreated.

Inactivation of pentraxin 3 suppresses M2-like macrophage activity and immunosuppression in colon cancer

BackgroundThe tumor microenvironment is characterized by inflammation-like and immunosuppression situations. Although cancer-associated fibroblasts (CAFs) are among the major stromal cell types in various solid cancers, including colon cancer, the interactions between CAFs and immune cells remains largely uncharacterized. Pentraxin 3 (PTX3) is responsive to proinflammatory cytokines and modulates immunity and tissue remodeling, but its involvement in tumor progression appears to be context-dependent and is unclear.MethodsOpen-access databases were utilized to examine the association of PTX3 expression and the fibroblast signature in colon cancer. Loss-of-function assays, including studies in tamoxifen-induced Ptx3 knockout mice and treatment with an anti-PTX3 neutralizing antibody (WHC-001), were conducted to assess the involvement of PTX3 in colon cancer progression as well as its immunosuppressive effect. Finally, bioinformatic analyses and in vitro assays were performed to reveal the downstream effectors and decipher the involvement of the CREB1/CEBPB axis in response to PTX3 and PTX3-induced promotion of M2 macrophage polarization.ResultsClinically, higher PTX3 expression was positively correlated with fibroblasts and inflammatory response signatures and associated with a poor survival outcome in colon cancer patients. Blockade of PTX3 significantly reduced stromal cell-mediated tumor development. The decrease of the M2 macrophage population and an increase of the cytotoxic CD8+ T-cell population were observed following PTX3 inactivation in allografted colon tumors. We further revealed that activation of cyclic AMP-responsive element-binding protein 1 (CREB1) mediated the PTX3-induced promotion of M2 macrophage polarization.ConclusionsPTX3 contributes to stromal cell-mediated protumor immunity by increasing M2-like macrophage polarization, and inhibition of PTX3 with WHC-001 is a potential therapeutic strategy for colon cancer.

P118 Pentraxin-3 interacts with Aspergillus fumigatus conidia to regulate pro-inflammatory cytokine production

Poster session 1, September 21, 2022, 12:30 PM - 1:30 PMObjectivesLong pentraxin-3 (PTX3) is a soluble pattern-recognition receptor secreted by phagocytes and non-immune cells at sites of inflammation. It has been reported to have a nonredundant role in the immune response against Aspergillus fumigatus. Indeed, PTX3 knock-out mice show an increased susceptibility to invasive pulmonary aspergillosis (IPA) with a higher mortality rate. In humans, PTX3 genetic deficiency or single nucleotide polymorphism has also been associated with an increased risk of IPA. However, the way in which PTX3 interacts with A. fumigatus and its mechanism of action has yet to be elucidated. The aim of the study was to investigate potential A. fumigatus ligands for PTX3 and the impact of A. fumigatus opsonization by PTX3 on modulating the immune response.Methods Aspergillus fumigatus conidia, the infective morphotype, were incubated with PTX3 with or without human serum, stained with anti-PTX3 antibody, and studied by immunofluorescence. Identification of potential fungal ligands for PTX3 was performed by ELISA. Fixed conidia and germinated conidia were opsonized with different serum factors and co-incubated with human monocyte-derived macrophages (hMDM) for 24 h at 37°C. Culture supernatants were collected, and pro-/anti-inflammatory cytokines were measured by sandwich ELISA.ResultsPTX3 did not bind A. fumigatus conidia directly but in the presence of human serum, purified collectins [surfactant protein D (SP-D) or C1q], and complement products (C3b). Pre-opsonization of conidia with these complement proteins or SP-D stimulated proinflammatory cytokine secretion by hMDM upon interaction (Fig. 1a). In contrast, secondary opsonization of complement proteins or SP-D opsonized conidia with PTX3 significantly reduced pro-inflammatory cytokines and increased anti-inflammatory cytokine secretion from hMDM. PTX3 opsonized PFA-fixed germinating conidia significantly reduced pro-inflammatory cytokine and increased anti-inflammatory cytokines secretion from hMDM (Fig. 1b).ConclusionPTX3 is an acute phase protein expressed in response to pro-inflammatory stimuli during infection and that is increased in bronchoalveolar lavage of patients with aspergillosis. Our recent data with A. fumigatus suggest that PTX3 is an immunoregulatory protein that reduces pro-inflammatory response. Although an inflammatory response is necessary to fight against fungal pathogens, the tissue damage associated with enhanced inflammation can be deleterious and facilitate A. fumigatus infection.

Pentraxin 3 and Shigella LPS and IpaB Antibodies Interplay to Defeat Shigellosis.

Shigella causes moderate to severe diarrhea or dysentery after invading the colon mucosa. Long Pentraxin 3 (PTX3) is recognized as the humoral component of the innate immune response to bacterial pathogens. We examined the interplay between levels of PTX3 and levels of anti-Shigella lipopolysaccharide (LPS) and anti-Shigella type 3 secretion system protein-IpaB antibodies in children during acute shigellosis and after recovery. PTX3 concentrations in serum and stool extracts were determined by sandwich ELISA using commercial anti-PTX3 antibodies. Serum IgG, IgM, and IgA anti-S. sonnei LPS or anti-S. sonnei IpaB were measured using in house ELISA. Children with acute shigellosis (n = 60) had elevated PTX3 levels in serum and stools as compared with recovered subjects (9.6 ng/mL versus 4.7 ng/mL, p < 0.009 in serum and 16.3 ng/g versus 1.1 ng/g in stool, p = 0.011). Very low levels of PTX3 were detected in stools of healthy children (0.3 ng/g). Increased serum levels of PTX3 correlated with high fever accompanied by bloody or numerous diarrheal stools characteristic of more severe shigellosis while short pentraxin; C-Reactive Protein (CRP) did not show such a correlation. PTX3 decreased in convalescence while anti-Shigella antibodies increased, switching the response from innate to adaptive toward the eradication of the invasive organism. These data can inform the development of Shigella vaccines and treatment options.

IgG anti-Pentraxin 3 antibodies are a novel biomarker of ANCA-associated vasculitis and better identify patients with eosinophilic granulomatosis with polyangiitis

ObjectiveTo investigate prevalence of anti-Pentraxin 3 (PTX3) antibodies in sera of anti-neutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) patients. MethodsAnti-PTX3 and PTX3 levels were analysed by enzyme-linked immunosorbent assays in sera from unselected patients with AAV and compared with patients with systemic lupus erythematosus (SLE, n = 130), other connective tissue diseases (CTDs, n = 97) and matched healthy controls (n = 97). Optical density (OD) cut-off for positive anti-PTX3 antibodies was determined by ROC curve analysis and set as 0.234. Indirect immunofluorescence (IIF) on fixed human granulocytes was used to analyze the fluorescence pattern of anti-PTX3 antibodies. Liquid-phase inhibition tests were conducted to assess potential interferences. ResultsWe included 101 AAV patients (females 58%, median age 60[51–69] years) affected either with granulomatosis with polyangiitis (GPA, n = 51), microscopic polyangiitis (MPA, n = 12) or eosinophilic granulomatosis with polyangiitis (EGPA, n = 38). Anti-PTX3 antibodies were detected in 29.7% AAV patients, being significantly higher than in healthy controls (p < 0.001) and CTDs (p = 0.030) but lower than in SLE (p = 0.004). Anti-PTX3 antibody prevalence was 44.7% in EGPA, 25% in MPA and 19% in GPA (p = 0.034). Among ANCA negative patients, 35.7% displayed positive anti-PTX3 antibodies. Anti-PTX3 were associated with a lower prevalence of systemic (p = 0.002), ear-nose-throat (p = 0.006) and renal manifestations (p = 0.016). Anti-PTX3 antibodies were characterized by a specific IIF pattern on fixed granulocytes. PTX3 serum levels resulted lower in AAV than healthy controls (p < 0.001). PTX3 inhibited anti-PTX3 binding in a dose-dependent manner. ConclusionsAnti-PTX3 autoantibodies appear a promising novel biomarker of AAV, especially EGPA.

Immunization with Pentraxin3 prevents transition from subclinical to clinical lupus nephritis in lupus-prone mice: Insights from renal ultrastructural findings

BackgroundPentraxin3 (PTX3) is an emerging player in lupus nephritis (LN). Anti-PTX3 antibodies showed to delay LN occurrence in vivo. AimTo evaluate renal changes following immunization with PTX3 in a murine model of LN. Materials and methodsTwenty-two lupus-prone New Zealand Black/White (NZB/W)F1 mice were divided into two groups (n = 11) and subcutaneously injected with human recombinant (hr)PTX3 100 μg or phosphate buffer saline (PBS) 200 μl, three times 3 weeks apart, starting before development of proteinuria. Five mice from each group were scheduled for sacrifice at week 22 and 6 from each group at week 29. Renal lesions included electron-dense deposits (EDD), glomerular deposition of IgG, complement and PTX3 as markers of renal inflammation. They were evaluated by immunofluorescence (IF), confocal and immunoelectron microscopy (IEM). Validated semiquantitative scores were used when available to score renal lesions. Chi-squared test with Fisher exact test was used for comparison. ResultsNineteen out of 22 mice were sacrificed as scheduled. Only hrPTX3-immunized mice developed anti-PTX3 antibodies. Compared to PBS-injected mice, they displayed a dramatic decrease in glomerular deposits of IgG, C1q and PTX3, as well as in the amount of EDD (p = 0.006) and podocyte effacement (p = 0.043). Importantly, PTX3 was pinpointed inside the EDD and co-localized with nuclear material. ConclusionsImmunization with PTX3 prevented progression from the preclinical to the clinical stage of LN, inciting anti-PTX3 antibodies and preventing renal PTX3 deposition. PTX3 is a novel component of EDD, submitting it as one initiating autoantigen in LN and as potential target for early treatment.

Circulating Pentraxin3-Specific B Cells Are Decreased in Lupus Nephritis.

Background: Pentraxin3 (PTX3) is overexpressed in kidneys of patients developing lupus nephritis (LN). Active LN is associated with reduced anti-PTX3 antibodies. However, abnormalities of B cell differentiation against PTX3 have not been characterized in systemic lupus erythematosus (SLE).Objective: Characterization of PTX3-specific (PTX3+) B cells in peripheral blood of SLE patients with or without LN and healthy donors (HD).Patients and Methods: SLE patients without LN, biopsy-proven LN and matched HD were analyzed. Active LN was defined as proteinuria>0.5 g/day or CrCl<60 ml/min/1.73 m2 with active urinary sediment. Peripheral B cells were analyzed for direct PTX3 binding by flow cytometry using PTX3 labeled with cyanine 5 (Cy5) and phycoerythrin (PE).Results: Initially, a flow cytometry based assay to identify PTX3+ B cells was developed by demonstrating simultaneous binding of PTX3-Cy5 and PTX3-PE. Specificity of B cells was validated by blocking experiments using unlabeled PTX3. We could identify circulating PTX3+ B-cells in HD and patients. Notably, LN patients showed a significantly diminished number of PTX3+ B cells (SLE vs. LN p = 0.033; HD vs. LN p = 0.008). This decrease was identified in naïve and memory B cell compartments (naïve: SLE vs. LN p = 0.028; HD vs. LN p = 0.0001; memory: SLE vs. LN p = 0.038, HD vs. LN p = 0.011).Conclusions: Decreased PTX3+ B cells in LN within the naïve and memory compartment suggest their negative selection at early stages of B cell development potentially related to a decreased regulatory function. PTX3+ B cells could candidate for autoantigen-defined regulatory B cells as a striking abnormality of LN patients.

Anticorps anti-pentraxine au cours des maladies auto-immunes

Pentraxins (PTXs) are soluble innate receptors belonging to the family of pattern recognition receptors (PRMs). PTXs are divided in two subfamilies based on structural characteristics: short and long PTXs. Short PTXs include C-reactive protein (CRP) and serum amyloid-P component (SAP), while long PTXs are mainly represented by PTX3. PTXs are implicated in various biological processes. Besides their anti-microbial function, PTXs are also involved in cellular debris and dying cell removal (efferocytosis). A tolerance breakdown towards PTXs has been observed in several autoimmune diseases such as systemic lupus erythematosus and ANCA-associated vasculitis. In the present review, in a first part, we summarize the main characteristics and biological functions of PTXs. In a second part, we review the knowledges on anti-PTX antibodies and their relationship with clinical features of auto-immune diseases. Anti-PTX3 antibodies are the matter of an in-depth review.

Impairment of PTX3 expression in osteoblasts: a key element for osteoporosis

Pentraxin 3 (PTX3) is a multifunctional glycoprotein regulating inflammatory response, cell proliferation and migration and deposition and remodelling of the extracellular matrix by a variety of cells. In this study, we investigated the possible role of PTX3 in bone homeostasis. To this end, we compared the expression and function of PTX3 in human osteoblasts of osteoporotic, osteoarthritic patients and young subjects not affected by bone diseases. Immunohistochemical analysis performed on bone head biopsies showed a close association between bone health and the number of osteoblasts expressing PTX3. Noteworthy, the proportion of PTX3-positive osteoblasts resulted to be significantly lower in osteoporotic patients compared with both young patients and osteoarthritic patients of the same age. Ex vivo culture of osteoblasts isolated from the three groups of patients confirmed in vivo observation. Specifically, we observed rare runt-related transcription factor 2 (RUNX2) immunopositive osteoblasts expressing PTX3 in cell cultures derived from osteoporotic patients and western blotting analysis showed 80% reduction of PTX3 in the corresponding culture extracts compared with young and osteoarthritic patients. The treatment of human osteoblast primary cultures derived from young patients with anti-PTX3 antibody dramatically affected osteoblast behaviour. Indeed, they lost the morphological and molecular features typical of mature osteoblasts, acquiring fibroblast-like shape and highly decreasing nuclear factor kappa-B ligand (RANKL) and RUNX2 expression. Also, the inhibition of PTX3 negatively affected osteoblast proliferation and their ability to form cell clusters and microhydroxyapatite crystals. Altogether, these results suggest a central role of PTX3 in bone homeostasis showing its involvement in osteoblast proliferation, differentiation and function.

Oleate-induced PTX3 promotes head and neck squamous cell carcinoma metastasis through the up-regulation of vimentin.

The association between metabolic diseases and the risk of developing cancer is emerging. However, the impact of long pentraxin-3 (PTX3) on dyslipidemia-associated tumor metastasis remains unknown. In this study, we found that oleate induced PTX3 expression and secretion through the activation of Akt/NF-κB pathway in head and neck squamous cell carcinomas (HNSCCs). The activation of NF-κB was essential for the oleate-induced stabilization of PTX3 mRNA. In addition, both the depletion of PTX3 and the inhibition of NF-κB significantly inhibited oleate-induced tumor cell migration and invasion. The enhancement of binding between tumor and endothelial cells was observed in oleate-treated cells but not in the depletion and neutralization of PTX3 with siPTX3 and anti-PTX3 antibodies, respectively. The levels of oleate-induced epithelial-mesenchymal transition (EMT) markers, such as vimentin and MMP-3, were significantly reduced in PTX3-depleted cells. Knocking down vimentin also repressed oleate-induced HNSCC invasion. Furthermore, the depletion of PTX3 blocked the oleate-primed metastatic seeding of tumor cells in the lungs. These results demonstrate that oleate enhances HNSCC metastasis through the PTX3/vimentin signaling axes. The inhibition of PTX3 could be a potential strategy for the treatment of dyslipidemia-mediated HNSCC metastasis.

Immunization with pentraxin 3 (PTX3) leads to anti-PTX3 antibody production and delayed lupus-like nephritis in NZB/NZW F1 mice

BackgroundAnti-pentraxin 3 (PTX3) antibodies were associated with the absence of lupus glomerulonephritis in humans. AimTo explore the effects of anti-PTX3 antibodies in New Zealand Black/White (NZB/NZW F1) mice and their inherent mechanisms of action. Materials and methods30 NZB/NZW F1 mice were subdivided into 3 groups of 10 mice each and subcutaneously injected with PTX3, alum and PBS (group 1), alum and PBS (group 2) or PBS alone (group 3), 3 times 3 weeks apart, before development of renal disease. Mice were followed until natural death. Histological analysis and immunohistochemistry were performed on harvested kidneys. Effects of anti-PTX3 antibodies on C1q binding to immobilized PTX3-anti-PTX3 immune complexes were evaluated in vitro using human SLE sera. Qualitative characterization of human IgG anti-PTX3 was performed. ResultsOnly group 1 mice developed anti-PTX3 antibodies. Anti-dsDNA and anti-C1q antibodies appeared significantly later and at lower levels in group 1 mice vs. controls (p < 0.0001). Proteinuria-free and overall survival were significantly increased in group 1 mice vs. controls (p < 0.05 and p = 0.03, respectively). Histopathological analysis showed that glomerular and tubular PTX3 staining and renal lesions were increased in controls compared with immunized mice.Addition of human SLE sera positive for anti-PTX3 antibodies to C1q and fixed PTX3 interfered with C1q binding to PTX3-anti-PTX3 immune complexes. Qualitative characterization of human IgG anti-PTX3 showed an increased proportion of IgG4. ConclusionsAnti-PTX3 antibodies delay lupus-like nephritis and prolong survival of NZB/NZW F1 mice. In vitro observations suggest anti-PTX3 antibodies may dampen complement activation via their Fc fragment, likely hindering renal inflammation.

PTX3, Anti-PTX3, and Anti-C1q Autoantibodies in Lupus Glomerulonephritis.

Pentraxin 3 (PTX3) is an acute-phase protein involved in C1q clearance. The presence of anti-C1q and the absence of anti-PTX3 antibodies were associated with lupus glomerulonephritis (LGLN). Our aim was to assess soluble and kidney-expressed PTX3 and their relationships with anti-C1q and anti-PTX3 antibodies in LGLN. Serum PTX3, anti-C1q, anti-dsDNA, and anti-PTX3 antibodies were tested in 130 systemic lupus erythematosus (SLE) patients, 130 healthy and 127 disease controls. Twenty-nine renal biopsies from SLE patients were analyzed and PTX3 immunostaining was quantified by morphometric analysis. Parametric and nonparametric statistics were performed. PTX3 serum levels were lower in SLE versus controls, but they were correlated with proteinuria in LGLN patients (p = 0.001). LGLN patients had higher anti-C1q and lower anti-PTX3 antibody levels than those without (p < 0.0001). LGLN was more prevalent in anti-C1q(+)/anti-PTX3(-) than in anti-C1q(+)/anti-PTX3(+) patients (p < 0.001). No LGLN was observed in anti-C1q(-)/anti-PTX3(+) patients. PTX3 was expressed in glomeruli and renal interstitium. Renal PTX3 was correlated with proteinuria (p = 0.024) and interstitial fibrosis (p = 0.023). PTX3 staining and fibrosis were higher in anti-PTX3(-) than anti-PTX3(+) patients. In conclusion, PTX3 is expressed in glomeruli of LGLN patients, primarily in anti-PTX3(-) patients, where it is correlated with renal fibrosis. Anti-C1q/anti-PTX3 antibody profile seems to be useful in LGLN assessment.

Pentraxin-3 Serum Levels Are Associated with Disease Severity and Mortality in Patients with Systemic Inflammatory Response Syndrome

The long pentraxin-3 (PTX3) is a key component of the humoral arm of the innate immune system. PTX3 is produced locally in response to pro-inflammatory stimuli. To investigate PTX3 levels and its use as a biomarker in patients with systemic inflammation, we developed a solid-phase enzyme-linked immunosorbent assay based on novel anti-PTX3 monoclonal antibodies detecting PTX3 with high sensitivity. The assay was applied on 261 consecutive patients admitted to an intensive care unit prospectively monitored with the systemic inflammatory response syndrome (SIRS). 100 blood donors were included as controls. PTX3 levels were elevated in patients (median = 71.3 ng/ml) compared with the controls (median = 0 ng/ml) (Mann-Whitney, p<0.0001). ROC analysis showed that PTX3 levels were significantly specific (85.0%) and sensitive (89.1%) to discriminate between healthy controls and patients (area under the curve (AUC) 0.922 (95% CI 0.892 to 0.946, p<0.0001)). Higher levels of PTX3 were associated with the development of sepsis, severe sepsis and septic shock (p = 0.0001). The serum levels of PTX3 correlated significantly with SAPS2 score (Spearman's rho 0.28, p<0.0001). Patients with high levels of PTX3 at admission did have a higher 90 day mortality rate than patients with the 25% lowest levels (Cox regression analysis, hazard ratio 3.0, p = 0.0009). In conclusion, we have established a highly sensitive and robust assay for measurement of PTX3 and found that its serum concentrations correlated with disease severity and mortality in patients with SIRS and sepsis.

Vaccination of mice for research purpose: alum is as effective as and safer than complete Freund adjuvant

Systemic lupus erythematosus (SLE) is an autoimmune disease involving many organ systems. Glomerulonephritis (GLN) is one of the major causes of morbidity and mortality in SLE. It has recently been demonstrated that adjuvants of vaccines could cause the so called ASIA syndrome. The study aimed to assess the effects of Complete Freund's Adjuvant (CFA) vs alum injections in NZB/NZWF1 mice. Mice (n=10 each group) were injected with a total volume of 200 μL of: CFA in PBS (group 1), alum in PBS (group 2), PBS (group 3) as controls, PTX3/CFA (group 4), PTX3/alum (group 5), 3 times, 3 weeks apart /given in each injection, three weeks apart from ten weeks of age. Urine samples were collected weekly to evaluate proteinuria. Blood samples were collected before every injection, at 21 weeks of age, and at death to evaluate levels of anti-PTX3 and anti-dsDNA. Proteinuria free survival and survival rates were analyzed by the Kaplan-Meier method using Mantel-Cox's test for comparisons. CFA-treated mice developed both anti-dsDNA antibodies and proteinuria earlier and at higher levels than alumtreated and PBS-injected mice, starting from 13 weeks of age. Proteinuria free survival rates (proteinuria ≥ 300 mg/dL) and survival rates were lower in CFA-treated mice than those treated with alum or injected with PBS (P<0.001 for all). No difference was observed between the alum-treated group and PBS-injected mice. Notably, groups 4 and 5, immunized with PTX3, developed anti-PTX3 antibodies and no significant difference was observed. Alum seems to be as effective as and safer than CFA as adjuvant, since it did not affect disease progression in immunized NZB/NZWF1 mice.

Pentraxin 3 as a new biomarker of peritoneal injury in peritoneal dialysis patients

It is well known that bioincompatible peritoneal dialysate plays a central role in the development of peritoneal fibrosis. Peritoneal inflammation continues even after the cessation of peritoneal dialysate stimulation. It is important to establish the definition of persistent inflammation in the peritoneal cavity at the cessation of peritoneal dialysis (PD). The objective of the present study was to determine whether pentraxin 3 (PTX3) in peritoneal effluent (PE) may be a new biomarker in PD patients. Serum, PE, and peritoneal specimens were obtained from 50 patients with end-stage kidney disease at Juntendo University Hospital. Samples of 19 patients were obtained at the initiation of PD and those of 31 patients at the cessation of PD. PTX3, high-sensitivity CRP, and MMP-2 and IL-6 were analyzed. An immunohistological examination using an anti-PTX3 antibody was performed. Expressions of PTX3 were observed in endothelial cells, fibroblasts, and mesothelial cells in the peritoneum. The PTX3 level in PE at the cessation of PD was significantly higher than that at the initiation of PD. Effluent PTX3 levels in patients with a history of peritonitis or a PD duration of more than 8 years were significantly higher than those in patients without peritonitis or patients with a PD duration of <8 years. The PTX3 level was significantly correlated with MMP-2 and IL-6 levels in PE, as well as the thickness of the submesothelial compact zone and the vasculopathy. It appears that PTX3 may be a new biomarker of peritoneal inflammation and progressive fibrosis.

IgG anti-pentraxin 3 antibodies in systemic lupus erythematosus

ObjectiveTo evaluate the prevalence and correlates of anti-pentraxin 3 (PTX3) antibodies in systemic lupus erythematosus (SLE).MethodsSerum samples from 130 patients with SLE, 130 age- and sex-matched healthy subjects and 130...

Abundance of the long pentraxin PTX3 at sites of leukocytoclastic lesions in patients with small‐vessel vasculitis

The prototypical tissue pentraxin PTX3 inhibits phagocytosis of late apoptotic polymorphonuclear leukocytes (PMNs) by macrophages. Levels of PTX3 parallel disease activity in small-vessel vasculitis. Small-vessel vasculitis is often characterized by leukocytoclasia, a phenomenon of accumulation of nuclear remnants from unscavenged PMNs in or near the vessel wall. We therefore hypothesized that PTX3 accumulates at sites of leukocytoclastic vasculitis and, as such, is a key factor for the induction of leukocytoclasis. We examined skin biopsy samples from 13 patients with small-vessel vasculitis and from 4 healthy and 3 inflammatory skin disease controls. Biopsy tissues, characterized histopathologically as leukocytoclastic vasculitis, were studied for the presence of PTX3 using rabbit anti-PTX3 polyclonal antibodies. Sections were scored morphometrically for leukocytoclastic infiltrates in conjunction with PTX3 staining. Morphometric scores were expressed as percentages of staining of the total tissue area. Biopsy specimens from patients with leukocytoclastic vasculitis revealed an abundant up-regulation of PTX3 at sites of leukocytoclastic infiltrates. Significantly more PTX3 was found in tissues from the 13 patients with vasculitis (mean +/- SEM 48.9 +/- 6.1%) than in tissues from the 7 controls (4.5 +/- 2.7%) (P = 0.0003). PTX3 was localized around vessels, as well as spread diffusely throughout the tissue. PTX3 is abundantly present at sites of leukocytoclastic infiltrates in patients with small-vessel vasculitis, but not in controls. Since PTX3 inhibits phagocytosis of late apoptotic PMNs by macrophages and is strongly up-regulated at sites of leukocytoclastic infiltration, PTX3 is a candidate factor in the phenomenon of leukocytoclasia in small-vessel vasculitis.