Clinical Characteristics of EGPA Patients in Comparison to GPA Subgroup with Increased Blood Eosinophilia from POLVAS Registry.

Objective: To characterize the eosinophilic granulomatosis with polyangiitis (EGPA) population from the POLVAS registry depending on ANCA status and diagnosis onset, including their comparison with the granulomatosis with polyangiitis (GPA) subset with elevated blood eosinophilia (min. 400/µl) (GPA HE) to develop a differentiating strategy. Methods: A retrospective analysis of the POLVAS registry. Results: The EGPA group comprised 111 patients. The ANCA-positive subset (n = 45 [40.54%]) did not differ from the ANCA-negative one in clinics. Nevertheless, cardiovascular manifestations were more common in ANCA-negative patients than in those with anti-myeloperoxidase (MPO) antibodies (46.97% vs. 26.92%, p = 0.045). Patients diagnosed before 2012 (n = 70 [63.06%]) were younger (median 41 vs. 49 years, p < 0.01), had higher blood eosinophilia at diagnosis (median 4,946 vs. 3,200/µl, p < 0.01), and more often ear/nose/throat (ENT) and cardiovascular involvement. GPA HE comprised 42 (13.00%) out of 323 GPA cases with reported blood eosinophil count. Both GPA subsets had a lower prevalence of respiratory, cardiovascular, and neurologic manifestations but more often renal and ocular involvement than EGPA. EGPA also had cutaneous and gastrointestinal signs more often than GPA with normal blood eosinophilia (GPA NE) but not GPA HE. The model differentiating EGPA from GPA HE, using ANCA status and clinical manifestations, had an AUC of 0.92, sensitivity of 96%, and specificity of 95%. Conclusion: Cardiovascular symptoms were more prevalent in the ANCA-negative subset than in the MPO-ANCA-positive one. Since EGPA and GPE HE share similarities in clinics, diagnostic misleading may result in an inappropriate therapeutic approach. Further studies are needed to optimize their differentiation and tailored therapy, including biologics.

Circulating Anti-Endothelial Cell Antibodies in Patients with Geographic Atrophy Related to Dry Age-Related Macular Degeneration.

Background and Objectives: Age-related macular degeneration (AMD) is one of the leading causes of central vision loss among elderly patients, and its dry form accounts for the majority of cases. Although several causes and mechanisms for the development and progression of AMD have previously been identified, the pathogenesis of this complex disease is still not entirely understood. As inflammation and immune system involvement are strongly suggested to play a central role in promoting the degenerative process and stimulating the onset of complications, we aimed to analyze the frequency of serum anti-retinal (ARAs) and anti-endothelial cell antibodies (AECAs) in patients with dry AMD and to determine their relationship with the clinical features of the disease, notably the area of geographic atrophy (GA). Materials and Methods: This study included 41 patients with advanced-stage dry AMD and 50 healthy controls without AMD, matched for gender and age. ARAs were detected by indirect immunofluorescence using monkey retina as an antigen substrate, and the presence of AECAs was determined using cultivated human umbilical vein endothelial cells and primate skeletal muscle. Results: ARAs were detected in 36 (87.8%) AMD patients (titers ranged from 1:20 to 1:320) and in 16 (39.0%) (titers ranged from 1:10 to 1:40) controls (p = 0.0000). Twenty of the forty-one patients (48.8%) were positive for AECAs, while in the control group, AECAs were present only in five sera (10.0%). The titers of AECAs in AMD patients ranged from 1:100 to 1:1000, and in the control group, the AECA titers were 1:100 (p = 0.0001). There were no significant correlations between the presence of AECAs and disease activity. Conclusions: This study demonstrates a higher prevalence of circulating AECAs in patients with dry AMD; however, no correlation was found between the serum levels of these autoantibodies and the area of GA.

Association between clinical features and course of systemic sclerosis and serum interleukin-8, vascular endothelial growth factor, basic fibroblast growth factor, and interferon alpha.

BACKGROUND: Certain mediators, such as soluble growth factors and cytokines, among others, are implicated in the immunopathogenesis of systemic sclerosis (SSc). OBJECTIVES: This study aimed to examine the association between serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), interferon alpha (IFN-α), and basic fibroblast growth factor (bFGF) and the clinical presentation and course of SSc. MATERIAL AND METHODS: This longitudinal, observational study included 43 patients with SSc and 24 healthy subjects. Serum concentrations of VEGF, IL-8, IFN-α, and bFGF were measured at baseline in patients previously treated for SSc. Medical history of patients was analyzed retrospectively at the time of cytokine measurement to infer clinical correlations, and during follow-up for a median of 5 years, assessing the incidence of death or cancer. RESULTS: The bFGF and IFN-α concentrations differed between SSc patients and controls (p < 0.01). In turn, organ involvement and SSc phenotypes did not impact studied cytokine concentrations, similar to systemic steroid and/or immunosuppressant use at enrollment. However, we have documented a positive correlation between the current oral steroid dose and serum levels of IL-8 and bFGF. Furthermore, patients with a VEGF level ≥95.7 pg/mL and IFN-α level ≥3.6 pg/mL required cyclophosphamide therapy more often, currently or in the past (approx. 3-fold and 4-fold, respectively). Substantially elevated VEGF and IFN-α concentrations at baseline were associated with higher cancer occurrence (n = 4) during follow-up, while elevated circulating IL-8 level was associated with an increased risk of death (n = 9). CONCLUSIONS: The SSc group was characterized by higher serum concentrations of bFGF and IFN-α compared to healthy controls. Patients treated with cyclophosphamide or receiving higher systemic steroid doses, thus suffering from a more severe disease type, had increased cytokine levels. Elevated circulating IFN-α and VEGF levels might be correlated with cancer, whereas raised IL-8 levels may be associated with an increased risk of death. However, further research is needed to verify our findings.

Autoimmune polyendocrine syndrome type 2 in patient with severe allergic asthma treated with omalizumab.

Asthma therapy with monoclonal antibodies is a promising and effective approach for those with a severe and refractory type of disease. Although such a targeted therapy is considered to be safe, unusual complications may occur. We present a case of a 45 year-old female patient with severe allergic asthma and chronic spontaneous urticaria, who developed autoimmune polyendocrine syndrome type 2 (APS-2) after 26 months of omalizumab administration. The patient was diagnosed with primary adrenal insufficiency (Addison's disease) and Hashimoto's thyroiditis accompanied by autoimmune atrophic gastritis. According to our knowledge this is the first description of APS-2 that developed in conjunction with omalizumab treatment, although we have no evidence that the observed phenomenon indicated a cause-effect relationship to omalizumab.

Serum anti-endothelial cell antibodies in patients with age-related macular degeneration treated with intravitreal bevacizumab.

PURPOSE: To analyse the prevalence and changes in circulating anti-endothelial cell antibodies (AECA) during anti-vascular endothelial growth factor (anti-VEGF) therapy. METHODS: Ninety-eight patients with exudative age-related macular degeneration (AMD) were treated with intravitreal bevacizumab. Fifty sex- and age-matched healthy subjects were used as controls. Serum AECA were detected using indirect immunofluorescence on primate skeletal muscle and cultivated human umbilical vein endothelial cells (HUVEC). These investigations were repeated at 4-week intervals within 8 months of follow-up. RESULTS: At baseline examination, 30 of the 98 patients (30.6%) were positive for AECA. The titres of AECA ranged from 1:10 to 1:320. In the control group, AECA were present in only nine sera (18%) with titres ranging between 1:20 and 1:80 (p = 0.0000). The greatest rates of reduction of AECA titres were observed during the 'loading' phase of therapy. During the 'maintenance' phase, the rates of changes in serum AECA levels were less significant and remained constant. In follow-up period in 13 patients (13.3%), serum AECA were detected de novo in titres of 1:10 to 1:80. Statistical analysis did not show any significant correlation between the presence of AECA and activity of the disease. CONCLUSIONS: There is growing evidence that AMD is an immune-mediated disease, and thus it cannot be excluded that AECA may be involved in its pathogenesis and progression. We also speculate that AECA develop in response to retinal damage and anti-VEGF therapy.

Circulating anti-retinal antibodies in response to anti-angiogenic therapy in exudative age-related macular degeneration.

PURPOSE: To determine changes in anti-retinal antibodies (ARAs) during anti-VEGF therapy in patients with exudative age-related macular degeneration (AMD) and to assess the correlations between ARAs and disease activity. METHODS: The study comprised 98 patients treated with intravitreal bevacizumab. The ophthalmic examination included best corrected visual acuity (BCVA), slit lamp biomicroscopy, fundoscopy, fluorescein angiography (FA), and optical coherence tomography (OCT). Serum ARAs levels were assessed by indirect immunofluorescence (IIF) on normal monkey retina substrate. These studies were repeated at 4 week intervals within 8 months of a follow-up. The sera of 50 sex- and age-matched healthy subjects were used as controls. RESULTS: At baseline examination, 94 (95.5%) of the 98 patients were positive for ARAs. The ARAs titres were significantly higher (p = 0.0000) than in controls. A positive correlation was found between titres of ARAs and the diameter of choroidal neovascularization (CNV) as measured by FA (p = 0.0000), and central retinal thickness (CRT) assessed by OCT (p = 0.0000). A positive correlation was also found between the diameter of CNV, CRT and the complexity of circulating ARAs. Following treatment all patients demonstrated significant decrease in ARAs levels as well as improvement of BCVA, reduction of subretinal fluid on OCT and decreased leakage on FA. CONCLUSION: Changes in serum ARAs levels occurred in parallel with clinical outcomes of anti-VEGF therapy. Treatment reduced serum levels of ARAs, with the greatest reduction occurring during the 'loading' phase. This study demonstrated that ARAs may act as a serum biomarker of the efficacy of anti-VEGF therapy.

Circulating antiretinal antibodies predict the outcome of anti-VEGF therapy in patients with exudative age-related macular degeneration.

PURPOSE: To determine serum antiretinal antibody (ARA) levels in response to treatment with intravitreal bevacizumab of exudative age-related macular degeneration (AMD). METHODS: The study comprised 22 patients treated with intravitreal bevacizumab (Avastin) 1.25mg. In all patients, serum ARA levels were assessed by indirect immunofluorescence on normal monkey retina substrate. The ophthalmic examination including best corrected visual acuity (BCVA), fundoscopy, fluorescein angiography, optical coherence tomography (OCT) and immunohistochemical investigations. These were repeated at 4-week intervals during a loading phase of antiangiogenic therapy. Sera of 22 sex- and age-matched healthy subjects were used as controls for immunohistochemical studies. RESULTS: Before bevacizumab therapy, ARAs were detected in the sera of all patients at titres ranging from 1:40 to 1:1280. The titres were significantly higher (p < 0.01) than in controls (1:10-1:40). There was no significant correlation between serum ARA titres and neither the type nor the dimensions of choroidal neovascularization, as well as central retinal thickness. Following treatment, all patients demonstrated significant decrease in ARA levels. This correlated with improvement of BCVA, decreased leakage of fluorescein and reduction of subretinal fluid on OCT. CONCLUSION: Serum ARA levels demonstrate a dynamic change which occurs in parallel with clinical outcomes of antiangiogenic therapy. They also may act as markers of the therapeutic benefits of vascular endothelial growth factor inhibition.

[Serum antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD) treated with transpupillary thermotherapy (TTT) alone and with transpupillary thermotherapy (TTT) combined with injection of triamcinolone acetonide (sTTA) under posterior Tenon's capsule]. / Przeciwciala przeciwsiatkówkowe (PPS) w surowicy chorych z wysiekowa postacia zwyrodnienia plamki zwiazanego z wiekiem (AMD) przed przezzreniczna termoterapia (TTT) oraz po przezzrenicznej termoterapii (TTT) laczonej z iniekcja octanu triamcinolonu pod tylna pochewke Tenona (sTTA).

PURPOSE: To assess serum level changes of antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD), treated with transpupillary thermotherapy (TTT) alone and with TTT combined with injection of triamcinolone acetonide (sTTA) under posterior Tenon's capsule and to compare the efficacy of TTT and TTT+sTTA. The purpose of the study was also to estimate if serum ARA may act as the biomarker of AMD. MATERIAL AND METHODS: This prospective study comprised 46 patients (46 eyes) with exudative AMD. Patients were assigned into: group I (n = 24) received TTT alone and group II (n = 20) received TTT with sTTA. Follow-up was at 3, 6, 9 and 12 months, when best-corrected visual acuity (BCVA), Amsler grid-test, intraocular pressure (IOP), fluorescein angiography (FA) and central retinal thickness (CRT) by optical coherence tomography (OCT) were assessed. In all patients serum ARA was determined using indirect immunofluorescence (IIF) method on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody. RESULTS: Baseline serum ARA titres in group I ranged from 1: 40 to 1: 5120 and in group II--1: 40 to 1: 1280 (p = 0.1). In control group serum ARA was present in 46.4% of sera in titres from 1: 10 to 1: 40. These differences were statistcally significant (p < 0.001). Nine fluorescence patterns of ARA were detected by IIF method in both groups of AMD patients, while control sera showed only three types of reaction. Statistically significant correlation was found between CNV size, CRT and serum ARA titres in both groups of patients (p < 0.01). In a follow-up period decreasing serum ARA titres were noted, specially for subjects treated with combined therapy, however it was not statistically significant at 3, 6 and 9 months while achieved significance (p < 0.01) at month 12. BCVA improvement or stabilization was observed in 64% of eyes in group I and in 75%--in group II (p = 0.1). No leakage on FA was found in 66.7% and 70% of cases, in group I and II, respectively (p = 0.01). CRT reduction was observed in 50% (group I) and in 70% (group II) of eyes (p = 0.01) at month 12. CONCLUSIONS: Our preliminary observations indicate that serum ARA changes may reflect the activity of CNV in a course of AMD and may act as the biomarker of treatment efficacy. The use of sTTA in conjunction with TTT for CNV in AMD showed a tendency towards lower serum ARA titres and better functional results after treatment as compared with eyes treated with TTT alone.

[Serum antiretinal antibodies (ARA) in patients with exudative age-related macular degeneration (AMD)--preliminary findings]. / Wystepowanie przeciwcial przeciwsiatkówkowych (PPS) w surowicy chorych z wysiekowa postacia zwyrodnienia plamki zwiazanego z wiekiem (AMD)--obserwacje wstepne.

BACKGROUND: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western world. Despite the magnitude of this clinical problem, the pathogenesis of the disease remains still unclear. AIM: To determine the tissue specificity and titer of antiretinal antibodies (ARA) in sera of patients with exudative AMD. MATERIAL AND METHODS: Forty-six patients (92 eyes) 16 males and 30 women with exudative AMD were stratified arbitrary into four groups of AMD activity/severity: group I (n = 19)--patients with active choroidal neovascularization (CNV) in one eye and with drusen in the other eye; group II (n = 14)--patients with bilateral CNV; group III (n = 10)--patients with CNV in one eye and with disciform scar in the contralateral eye; group IV (n = 3)--patients with bilateral disciform scars. In all patients serum ARA were determined using indirect immunofluorescence detection on normal monkey retina as antigens substrate and FITC--labelled goat's anti-human IgA, G, M serum as the secondary antibody. RESULTS: In all patients' serum ARA were present in the range of titres from 1:40 to 1:5120. Control sera (n = 28, 28 males) demonstrated the presence of ARA in titres 1:10 to 1:40 in 46.4% cases. High serum titres of ARA characterized AMD patients with bilateral CNV and CNV in one eye and drusen in the contralateral eye. Low titres of ARA were detected in serum of patients with bilateral disciform scars. Indirect immunofluorescence (IIF) showed eight types histological patterns of patients' sera reactivity against retinal tissue. No correlation was found between serum ARA type and macular lesion activity. CONCLUSIONS: Our preliminary observations indicate a common presence of various ARA in serum of patients with AMD. Thus, it cannot exclude that ARA are involved in the pathogenesis or progression of AMD.

[Antiphospholipid syndrome in autoimmune diseases]. / Zespól antyfosfolipidowy w przebiegu chorób autoimmunologicznych.

Classification criteria for antiphospholipid syndrome were first proposed in 1987, revised in 1999 (Sapporo criteria) and up-dated in 2006. The aim of the study was to analyze associations between clinical and laboratory symptoms of antiphospholipid syndrome in the group of patients with autoimmune diseases, based on recently up-dated classification criteria. 336 patients were enrolled into the study, with the majority (n=235) suffering from SLE. Laboratory determinations included: lupus anticoagulant (LA), anticardiolipin (aCL) and anti-beta2-glycoprotein I (abeta2GPI) (both of IgG and IgM class). Clinical and laboratory symptoms of antiphospholipid syndrome were quite common among patients studied. There was a significant association between laboratory and clinical features of antiphospholipid syndrome, according to recently modified classification criteria.

[Sicca syndrome and pulmonary fibrosis in a woman with anti-RO and anti-Jo-1 antibodies]. / Zespól suchosci oraz zwlóknienie pluc u pacjentki z przeciwcialami anty-Ro i anty-Jo-1.

We describe a case of a 52-year old woman with clinical and immunological features of sicca syndrome associated with pulmonary fibrosis, anti-Jo-1, and anti-Ro-52 antibodies but without any signs of idiopathic inflammatory myopathy.