Complement C1s deficiency in a male Caucasian patient with systemic lupus erythematosus: a case report.

Deficiencies of the early complement components of the classical pathway (CP) are well-documented in association with systemic lupus erythematosus (SLE) or SLE-like syndromes and severe pyogenic infections. Among these, complete C1s deficiency has been reported in nine cases so far. Here, we describe a 34-year-old male patient who presented with severe, recurrent infections since childhood, including meningitides with pneumococci and meningococci, erysipelas, subcutaneous abscess, and recurrent infections of the upper airways.

Methotrexate Treatment Suppresses Monocytes in Nonresponders to Pneumococcal Conjugate Vaccine in Rheumatoid Arthritis Patients.

Patients with rheumatoid arthritis (RA) have an increased risk of infections; therefore, immunization against vaccine-preventable diseases is important. Methotrexate (MTX) impairs the antibody response to pneumococcal conjugate vaccine (PCV) in patients with arthritis, and the underlying mechanism is largely unknown. Here, we investigate the potential role of the innate immune system in the faltering antibody response following PCV vaccination in RA patients treated with MTX.

Comorbidities in hereditary angioedema-A population-based cohort study.

Background: In hereditary angioedema (HAE), low levels (type 1) or defect in function (type 2) of the serine-protease inhibitor C1 Inhibitor protein results in activation of the classical pathway of the complement system as well as the contact system. Here, we investigated the risk of comorbidities in HAE.

Methods: Individuals with HAE (n = 239; identified through a physician made diagnosis) and a control cohort from the general population (n = 2383; matched for age, gender, and county of residence) were compared with the Swedish inpatient, cause of death, cancer, and prescription registers.

Methotrexate reduces circulating Th17 cells and impairs plasmablast and memory B cell expansions following pneumococcal conjugate immunization in RA patients.

Methotrexate (MTX) impairs antibody response after pneumococcal vaccination. We aimed to investigate differences in phenotypes of circulating B and T cells after pneumococcal conjugate vaccine (PCV) in rheumatoid arthritis (RA) patients on MTX (MTX group), RA without disease-modifying drugs (0DMARD), and controls (HC). MTX group (n = 11), 0DMARD (n = 12) and HC (n = 13) were studied.

Increased serum bactericidal activity of autologous serum in C2 deficiency after vaccination against Haemophilus influenzae type b, and further support for an MBL-dependent C2 bypass mechanism.

Deficiencies of C2 and other components of the classical pathway of complement are associated with increased risk of infections with encapsulated bacteria, such as Haemophilus (H.) influenzae. Defense against H.

Increased Frequencies of Switched Memory B Cells and Plasmablasts in Peripheral Blood from Patients with ANCA-Associated Vasculitis.

B cells are thought to play a central role in the pathogenesis of antineutrophil cytoplasmic antibody- (ANCA-) associated vasculitis (AAV). ANCAs have been proposed to cause vasculitis by activating primed neutrophils to damage small blood vessels. We studied a cohort of AAV patients of which a majority were in remission and diagnosed with granulomatosis with polyangiitis (GPA).

Correction to: Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients.

An amendment to this paper has been published and can be accessed via the original article.

Prime-boost vaccination strategy enhances immunogenicity compared to single pneumococcal conjugate vaccination in patients receiving conventional DMARDs, to some extent in abatacept but not in rituximab-treated patients.

Objective: To explore whether a prime-boost vaccination strategy, i.e., a dose of pneumococcal conjugate vaccine (PCV) and a dose of 23-valent polysaccharide vaccine (PPV23), enhances antibody response compared to single PCV dose in patients with inflammatory rheumatic diseases treated with different immunosuppressive drugs and controls.

[Hypocomplementemic urticarial vasculitis syndrome: a rare but not always benign condition].

Although more than 45 years have passed since hypocomplementemic urticarial vasculitis (HUVS) was first described by McDuffie and colleagues at the Mayo clinic, data on epidemiology, disease outcomes, prognosis and clinical features are scarce. Recently, we published the first epidemiological study of HUVS including data on incidence, prevalence, disease outcomes, prognosis and clinical features using data from two separate Swedish regions during a period of 16 years. The estimation of incidence and prevalence rates indicates that HUVS is rare but not always benign.

Clinical Complement Analysis-An Overview.

The complement system plays an important role in varying types of disease, ranging from inflammatory and autoimmune disorders to immune deficiency states. In addition, new settings have emerged where complement analysis is of interest to monitor complement-directed therapy and aid identification of transplant complications. Therefore, it is critical that clinical laboratories offer optimized and timely complement analysis.

Neutrophils from ANCA-associated vasculitis patients show an increased capacity to activate the complement system via the alternative pathway after ANCA stimulation.

Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV), including granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA), are autoimmune conditions associated with small vessel inflammation. Earlier studies indicate that complement activation via the alternative pathway plays a major role in the pathogenesis. In this study we have investigated if ANCA-activation of neutrophils from AAV patients leads to activation of the alternative complement pathway.

Antibody response to 13-valent pneumococcal conjugate vaccine is not impaired in patients with rheumatoid arthritis or primary Sjögren's syndrome without disease modifying treatment.

Background: Pneumococcal vaccination is recommended to patients with rheumatoid arthritis (RA) and primary Sjögren's syndrome (pSS). However, little is known whether the diseases influence pneumococcal vaccine response. This study aimed to investigate antibody response and functionality of antibodies following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in RA patients or pSS patients without disease modifying anti-rheumatic drugs (DMARD), compared to patients with RA treated with DMARD or to healthy controls.

Evaluation of a Novel Immunoassay for Quantification of C1q for Clinical Diagnostic Use.

C1q is a valuable biomarker of disease activity in systemic lupus erythematosus (SLE). The "gold standard" assay, rocket immunoelectrophoresis (RIE), is time-consuming, and thus a shift to soluble immune precipitation techniques such as nephelometry has occurred. However, quantification of C1q with these techniques has been questioned as a result of the antibody binding properties of C1q.

Inherited Classical and Alternative Pathway Complement Deficiencies in Children: A Single Center Experience.

Background: Primary complement deficiencies are rare diseases.

Objective: To retrospectively evaluate the clinical and laboratory findings and complications of patients to increase awareness of pediatricians about complement deficiencies, which are rarely encountered.

Methods: In this study, the clinical and immunological characteristics of 21 patients who consulted the Immunology Department of our hospital between 2003 and 2017 and were diagnosed with classical or alternative pathway complement deficiency were obtained from the file records.

Analysis of Anti-C1q Autoantibodies by Western Blot.

Anti-C1q autoantibodies may be found in many conditions, most commonly in systemic lupus erythematosus (SLE) and hypocomplementemic urticarial vasculitis syndrome (HUVS), and are diagnostic markers as well as disease activity markers in lupus nephritis. Sera from patients with SLE and HUVS show partly distinct autoantibody reactivities to separated protein chains B and C of the first component of complement, C1q. These different binding specificities can be detected by Western blot analysis of the autoantibodies under reducing conditions.

Analysis of C3 Nephritic Factors by ELISA.

Autoantibodies to the C3 convertase of the alternative pathway of complement, called C3 nephritic factors (C3NeF), cause persistently low C3 in the circulation and production of C3 degradation fragments due to prolonged stabilization of the C3 convertase. C3NeF are associated with glomerulopathy, acquired partial lipodystrophy, and less frequently with increased susceptibility to meningococcal infection. Analysis of C3NeF is an important part of the diagnostic workup of C3 glomerulopathy, but their identification is difficult presumably due to considerable heterogeneity.

Interpretation of Serological Complement Biomarkers in Disease.

Complement system aberrations have been identified as pathophysiological mechanisms in a number of diseases and pathological conditions either directly or indirectly. Examples of such conditions include infections, inflammation, autoimmune disease, as well as allogeneic and xenogenic transplantation. Both prospective and retrospective studies have demonstrated significant complement-related differences between patient groups and controls.

Epidemiology of hypocomplementaemic urticarial vasculitis (anti-C1q vasculitis).

Objectives: The aim was to describe the clinical characteristics and epidemiology of hypocomplementaemic urticarial vasculitis (HUV; anti-C1q vasculitis) in two geographically defined areas of Sweden.

Methods: In the health-care districts surrounding Skåne University Hospital (mean population 950 560) and Linköping University Hospital (mean population 428 503), all incident cases of HUV residing within the study areas at the onset of disease were identified during the years 2000-15. The diagnosis of HUV was confirmed by review of medical records.

Low Levels of Immunoglobulins and Mannose-Binding Lectin Are Not Associated With Etiology, Severity, or Outcome in Community-Acquired Pneumonia.

Background: Disease severity and outcome in community-acquired pneumonia (CAP) depend on the host and on the challenge of the causal microorganism(s). We measured levels of immunoglobulins (Igs) and complement in 257 hospitalized adults with CAP and examined the association of low levels of Igs or complement to microbial etiology, disease severity, and short-term and long-term outcome.

Methods: Serum Igs were analyzed in blood samples obtained at admission and at 6 weeks postdischarge if admission levels were low.

Immunogenicity and safety of pneumococcal vaccination in patients with systemic sclerosis.

Objective: To study the impact of disease and treatment with DMARDs on antibody response elicited by either pneumococcal conjugate vaccine (PCV13) or pneumococcal polysaccharide vaccine (PPV23) in patients with SSc.

Methods: Forty-four SSc patients and 49 controls received a dose of either PCV13 or PPV23. Twelve patients were treated with DMARDs.

Immune response to pneumococcal conjugate vaccine in patients with systemic vasculitis receiving standard of care therapy.

Aim: To study the effect of standard of care therapy on antibody response and functionality following immunization with 13-valent pneumococcal conjugate vaccine (PCV13) in patients with primary systemic vasculitis compared to healthy controls.

Methods: 49 patients with vasculitis and 49 controls received a single dose (0.5ml) PCV13 intramuscularly.