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Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(®)) in immunodeficiency patients. We collected retrospective data from 30 patients with primary and secondary immunodeficiency diseases in therapy with fSCIG from September 2014 to December 2019. We evaluated the efficacy of the therapy, taking into account serum IgG values during follow-up and the number of annual infectious events and serious bacterial infections reported by patients. Safety was assessed on the basis of the number and intensity of adverse events (AEs) and local reactions reported. Our real-life data suggest that long-term repeated self-administration of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulins results in a reduced rate of infectious events if compared to the pre-treatment rate. Both AEs and local reactions are mild to moderate and were never reasons for treatment discontinuation. Therapy with HyQvia shows prolonged efficacy and good tolerability; these aspects, together with the possibility of self-administration at home, minimize the impact the illness has on patients.

Chronic urticaria (CU) is a mast cell-driven disease characterized by the development of wheals, angioedema, or both for more than 6 weeks. The two major sub-types are chronic spontaneous urticaria (CSU) and inducible urticaria. In the last decade different pathophysiological mechanisms, potentially responsible for the development of the disease, have been described. It is likely that the activation of mast cells and basophils in CSU can be the results of immune system dysregulation, activation of the inflammatory cascade, and of the extrinsic coagulation pathway. Some of the mediators involved in the pathophysiological mechanisms of CSU have recently been identified as potential biomarkers useful for the diagnosis, follow-up, and management of the disease, even if they are not yet available in clinical practice. Thus, in this review we discuss new insights in the mediators involved in the pathogenesis of CSU, highlighting their potential role as biomarkers in the activity and progression of the disease and response to therapies.

Objective Glucocorticoids (GC) are associated with side effects in giant cell arteritis (GCA). Immunosuppressive therapies (ITs) have given conflicting results in GCA, regarding GC sparing effect. Primary endpoint is to evaluate whether very early introduction of ITs in GCA minimize the rate of GC-induced adverse events, in terms of infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures. Methods A multicenter retrospective case-control study included 165 patients. One group included 114 patients who were treated with at least one IT given at diagnosis or within 3 months from the start of GC. A second group included 51 GCA who received only GC or an IT more than 3 months later. Results The most frequently used ITs were: methotrexate (138 patients), cyclophosphamide (48 patients) and tocilizumab (27 patients). No difference was observed as concerns the follow-up time between groups [48.5 (IQR 26–72) vs 40 (IQR 24–69), p ​= ​0.3)]. The first group showed a significantly lower incidence of steroid-induced diabetes (8/114, 7% vs 12/51, 23.5%; p ​= ​0.003) and no differences for the rate of infections (p ​= ​0.64). The group was also exposed to lower doses of GC at first (p ​, Highlights • Giant cell arteritis is still a glucocorticoid-dependent disease. • Very early introduction of immunosuppressive agents minimizes the use of glucocorticoids. • Incidence of diabetes could be decreased by this strategy. • Safety in the elderly seems to be guaranteed.

Humoral immunodeficiency diseases represent a heterogeneous group of disorders that require long-term therapies. Thus, the treatment provided must not only be effective but also safe and well tolerated. In this paper, we report our data on the efficacy, safety, and tolerability of recombinant human hyaluronidase-facilitated subcutaneous infusion of immunoglobulin (Ig) (fSCIG; HyQvia(

Background:Glucocorticoids (GC) are associated with serious side effects in giant cell arteritis (GCA). Immunosuppressive therapies (IT) gave conflicting results in GCA, regarding GC sparing effect. Recently, tocilizumab by blocking IL-6, has been licensed as first biologic treatment for GCA, being clinically effective and saving GC (1).Objectives:To evaluate the usefulness of IT for GCA in: 1) minimizing the rate of GC-induced adverse events (AEs) and 2) reducing the risk of relapse.Methods:A multicenter retrospective case-control study included 165 GCA was performed. The first group of patients (GCA-IT) included 114 patients who were treated with at least one IT given ab initio or within 3 months from the start of GC. The control group included 51 GCA who received only GC or an IT later than 3 months (GCA-steroid). The primary endpoints were the rate of GC-related side effects: infections, hospitalized infections, new onset systemic arterial hypertension, GC-induced diabetes and osteoporotic fractures.Results:Methotrexate up to 20 mg/week (138 patients), followed by cyclophosphamide (48 patients) and tocilizumab (27 patients) were the most frequently used IT. No difference was observed as concerns the follow-up time between the two groups [48.5 (IQR 26-72) vs 40 (IQR 24-69), p=0,3, rank-sum test)]. The two groups were similar as concerns sex (p=0,13), while the first group (69±8 yrs) was slightly younger than the second one (72±7 yrs) (p=0,005). Comorbidity was similar between groups. Patients in the GCA-IT group showed a significant lower incidence of GC-induced diabetes (8/114, 7% vs 12/51, 23,5%; p=0,003, chi-square test), while no differences were documented for rate of infections (p=0,64), including hospitalized infections (p=0,44), new onset systemic arterial hypertension (p=0,68), or osteoporotic fractures (p=0,32). Forty-four patients in the GCA-IT group (38,6%), while 34 patients in the GCA-steroid group (66,7%) experienced at least one relapse (p=0,001, chi square test). There was no difference in terms of time to first relapse between the two groups (p=0,53, log-rank test). GCA-IT group was exposed to lower dose of GC at first (pConclusion:Very early introduction of IT in GCA provided a greater steroid sparing in the first 3 months of treatment, leading to a lower incidence of diabetes. Relapse rate was even lower. IT was usually well tolerated without an increase incidence of infections. A randomized prospective trial is required to support this strategy in the management of GCA.References:[1]Hellmich B, et al. 2018 Update of the EULAR recommendations for the management of large vessel vasculitis. Ann Rheum Dis. 2020;79:19-30.Disclosure of Interests:Luca Quartuccio Consultant of: Abbvie, Bristol, Speakers bureau: Abbvie, Pfizer, Miriam Isola: None declared, Dario Bruno: None declared, Elena Treppo: None declared, Laura Gigante: None declared, Francesca Angelotti: None declared, Riccardo Capecchi: None declared, Gianfranco Vitiello: None declared, Elena Cavallaro: None declared, Antonio Tavoni: None declared, Silvia Laura Bosello: None declared, Daniele Cammelli: None declared, Salvatore De Vita Consultant of: Roche, GSK, Speakers bureau: Roche, GSK, Novartis, Elisa Gremese Speakers bureau: Abbvie, BMS, Celgene, Jannsen, Lilly, MSD, Novartis, Pfizer, Sandoz, UCB

Background Glucocorticoids (GC) remain the mainstay of treatment of giant cell arteritis (GCA). However, relapses occur in up to 50% of patients when GC are tapered and prolonged courses of GC are associated with serious side effects. In this setting, the outcome is frequently determined by GC-related adverse events (AEs). Thus, several studies have been conducted on the effectiveness of a GC-sparing immunosuppressive therapy (IT), with conflicting results. Objectives To evaluate the effectiveness of IT in a series of GCA patients, in: 1) reducing the risk of GCA relapse; 2) lowering the exposure to GC therapy; 3) minimising the occurrence of steroid-induced AEs. Methods We performed a multicenter retrospective observational study including 69 patients (75,4% females; mean age ±SD 68,7±7,8 y; median follow-up time 40 months [range 26–65]) diagnosed with GCA, all receiving an adjunctive IT given ab initio (71%) or within 3 months from the start of GC. All but 17 patients (with extracranic involvement) fulfilled the GCA ACR classification criteria. Risk of first relapse of GCA, GC exposure and main AEs were retrospectively analysed. Results were compared with those reported in other studies, all characterised by a lower use of IT. Results all patients received GC plus IT: methotrexate up to 20 mg/week in 63 patients, cyclophosphamide in 22, tocilizumab in 12. In the follow-up, a first relapse of GCA occurred in 14 (20,3%) of patients. The rates of first relapse at 12, 24, 36 and 48 weeks were 4,3%, 11,6%, 15,9% and 15,9%, respectively, in comparison with rates of 24,3%, 41,6%, 61%, 64,9%, respectively, in the GC monotherapy arm in the meta-analysis by Mahr,1 where similar data were available. The median daily prednisone dose at beginning was 50 mg, and decreased to 10 mg at 3 months and to 5 mg at 6 months. The median time required to reduce prednisone to 7.5 mg/day and 5 mg/ was 3 and 5 months respectively (vs. 6.5 and 7.5 months in series by Proven,2 where similar data were available). In our cohort, lower cumulative GC use was accompanied by a reduction of AEs, without further toxicity (tab.1). Conclusions The use of IT ab initio or very early in the treatment of GCA appears to be effective and safe, lowering the risk of relapses, reducing GC dose and the rate of GC-related AEs. Therefore, the present data support the early introduction of IT in the treatment of GCA. References [1] Mahr AD, et al. Arthritis Rheum2007;56(8):2789–97. [2] Proven A, et al. Arthritis Rheum 2003 49(5):703–8.[3] Souza AW, Okamoto KY, Abrantes F, et al. Clinics (Sao Paulo) 2013;68:317–322.[4] Alba MA, et al. Medicine (Baltimore) 2014;93(5:194–201.[5] Labarca C, et al. Rheumatology (Oxford) 2016;55(2:347–56.Disclosure of Interest: None declared

Background: Dysregulated production of cytokines has a critical role in systemic lupus. The aim of this work is to identify, by a comprehensive analysis of IL-1 family cytokines and receptors in serum, correlation between cytokines/receptors' levels and the clinical and serological features of the disease.Methods: A full clinical evaluation was performed in 74 patients with systemic lupus erythematosus (SLE). C3, C4, anti-dsDNA and anti-C1q antibodies were measured. Cytokines of the IL-1 family (IL-1α, IL-1β, IL-33, IL-18), soluble receptors (sIL-1R1, sIL-1R2, sIL-1R3, ST2/sIL-1R4) and antagonists (IL-1Ra, IL-18 binding protein (IL-18BP)) were measured in serum by multiarray ELISA. Free IL-18 was calculated as the amount of IL-18 not inhibited by IL-18BP. Data were analysed by non-parametric tests and by multivariate analysis, using partial least squares (PLS) models.Results: Total IL-18, IL-18BP, sIL-1R4 and IL-1Ra levels were higher in SLE vs. controls. Total and free IL-18 and sIL-1R4 were higher in patients with active vs. inactive disease and correlated with ECLAM, anti-C1q and anti-dsDNA antibodies. sIL-1R2 was higher in patients with inactive disease, was negatively correlated with ECLAM and anti-C1q antibodies and was positively correlated with C3 levels. PLS identified sIL-1R4, sIL-1R2 and anti-dsDNA as variables distinguishing patients with active from those with inactive disease; sIL-1R4, IL-18BP and anti-dsDNA identified patients with active nephritis; sIL-1R4, C3, IL-18 and free IL-18 identified patients with haematological involvement.Conclusion: The data support the use of IL-18, sIL-1R2 and sIL-1R4 as biomarkers of disease activity and organ involvement, and suggest that failure in the inhibition of IL-1 activation may be a critical event in the active stages of SLE.

Background The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of systemic lupus erythematosus (SLE) patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (Crithidia Luciliae immunofluorescence test (CLIFT)). To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae minicircles, complexed with histone peptides. Methods Electrically neutral complexes of PK201/CAT plasmid (PK) DNA and histone 4 (H4) peptides were evaluated by electromobility shift assay. Complexes of H4 peptides and PK were absorbed to the solid phase to detect specific immunoglobulin G (IgG) in sera. Sera from 109 SLE patients, 100 normal healthy subjects, and 169 disease controls were tested. Results H4(14-34) containing the consensus sequence for DNA binding interacts with PK, retarding its migration. H4(14-34)/PK complexes were used to test sera by ELISA. Anti-H4-PK antibodies were detected in 56 % of SLE sera (more frequently in patients with skin or joint involvement) versus 5.9 % in disease controls; inhibition assays show that sera react with epitopes present on DNA or on the complex, not on the peptide. Antibody titer is correlated with European Consensus Lupus Activity Measurement (ECLAM) score and anti-complement component 1q (C1q) antibodies, negatively with C3 levels. Anti-H4-PK antibodies compared with CLIFT and solid phase dsDNA assays display moderate concordance. Conclusions The H4/PK assay is a simple and reliable test which is useful for the differential diagnosis and evaluation of disease activity in SLE patients. Electronic supplementary material The online version of this article (doi:10.1186/s13075-016-1117-8) contains supplementary material, which is available to authorized users.

Background The detection of anti-dsDNA antibodies is critical for the diagnosis and follow-up of SLE patients. The presently available assays are characterized by a non-optimal specificity (solid phase assays) or sensitivity (CLIF test). Objectives To overcome the limits of CLIFT and solid phase chromatin assays, we explored the diagnostic potential of an assay based on plasmid DNA containing a highly bent fragment of 211 bp from Crithidia Luciliae microcircles, complexed with histone peptides. Methods Electrically neutral complexes of PK201/CAT plasmid (PK) DNA and histone (H) 4 peptides were evaluated by electromobility shift assay. Complexes of H4 peptides and PK were absorbed to the solid phase to detect IgG antibodies in sera. Sera from 109 SLE patients, 100 normals and 69 disease controls (systemic sclerosis, Sjogren9s syndrome, unclassified connective tissue disease) were tested. Results H4 (14–34) containing the consensus sequence for DNA binding interacts with PK retarding its migration. H4 (14–34)-PK complexes were used to test sera by ELISA; inhibition assays show that sera react with epitopes present on DNA or on the complex, not on the peptide. Anti-H4-PK antibodies were detected in 56% SLE sera (more frequently in patients with skin or joint involvement) vs 12% disease controls; antibody titer is correlated with ECLAM score and anti-C1q antibodies, negatively with C3 levels. Anti-H4-PK antibodies compared with CLIFT and solid phase dsDNA assays display moderate concordance. Conclusions The H4-PK assay is a simple and reliable test, endowed with high specificity and sensitivity, useful for the differential diagnosis and evaluation of disease activity of SLE patients. This assay increases the variety of anti-DNA antibodies that can be measured, complementing the assays currently used for the detection of anti-DNA antibodies. Disclosure of Interest None declared