Mannose-binding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjogren's syndrome

Ramos-Casals, Manuel; Brito-Zerón, Pilar; Soria, Natalia; Nardi, Norma; Vargas, Alfonso; Muñoz, Sandra; Bové, Albert; Suárez, Belén; Lozano, Francisco

doi:10.1093/rheumatology/ken411

Cited by 20 publications

(14 citation statements)

References 45 publications

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“…In this context, mice lacking such bridging molecules, such as MFG-e8, Mer or C1q are reported to develop lupus-like manifestations associated with inefficient removal of apoptotic cells [32] . In line to these observations, several quantitative and functional aberrations of the above opsonins have been described in SLE and SS patients, including hypocomplementemia, which is considered as one of the major immunological markers and of key clinical importance for both disorders [44] , [45] . In fact, an intact classical complement pathway is essential for the phagocytic removal of apoptotic cells [46] , whereas the deficient ApoCell-phagocytosis in SLE patients has been previously attributed to defective opsonization of apoptotic cells by aberrantly low levels of C1q, C3, and C4 complement proteins [17] .…”

Section: Discussionmentioning

confidence: 67%

Impaired Clearance of Early Apoptotic Cells Mediated by Inhibitory IgG Antibodies in Patients with Primary Sjögren's Syndrome

et al. 2014

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ObjectivesDeficient efferocytosis (i.e. phagocytic clearance of apoptotic cells) has been frequently reported in systemic lupus erythematosus (SLE). Todate, patients with primary Sjögren's syndrome (SS) have not been assessed for phagocytosis of apoptotic cells (ApoCell-phagocytosis) and of particulate targets (microbeads, MB-phagocytosis).DesignApoCell-phagocytosis and MB-phagocytosis were comparatively assessed by flow cytometry in peripheral blood specimens and monocyte-derived macrophage (MDM) preparations from healthy blood donors (HBD) and consecutive SS, SLE and rheumatoid arthritis (RA) patients. Cross-admixture ApoCell-phagocytosis experiments were also performed using phagocytes from HBD or patients, and apoptotic cells pretreated with whole sera or purified serum IgG derived from patients or HBD.ResultsCompared to HBD, approximately half of SS and SLE patients studied (but not RA) manifested significantly reduced ApoCell-phagocytosis (p<0.001) and MB-phagocytosis (p<0.003) by blood-borne phagocytes that correlated inversely with disease activity (p≤0.004). In cross-admixture assays, healthy monocytes showed significantly reduced ApoCell-phagocytosis when fed with apoptotic cells that were pretreated with sera or purified serum IgG preparations from SS and SLE patients (p<0.0001, compared to those from HBD or RA). Such aberrant effect of the SS and SLE sera and IgG preparations correlated linearly with their content of IgG antibodies against apoptotic cells (p≤0.0001). Phagocytic dysfunction maybe also present in certain SS and SLE patients, as supported by deficient capacity of MDM for ApoCell-phagocytosis and MB-phagocytosis under patients' serum-free conditions.ConclusionSimilarly to SLE, efferocytosis is frequently impaired in SS and is primarily due to the presence of inhibitory IgG anti-ApoCell antibodies and secondarily to phagocytes' dysfunction.

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Section: Discussionmentioning

confidence: 67%

Impaired Clearance of Early Apoptotic Cells Mediated by Inhibitory IgG Antibodies in Patients with Primary Sjögren's Syndrome

et al. 2014

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“…The first description of MASP2 polymorphisms was made in 2003 (Stengaard-Pedersen et al, 2003), in a patient with invasive pneumococcal infection and autoimmune disease who carried MASP2 p.D371 and p.D120G polymorphisms (in addition to MBL2 B allele). Since then, a few other studies have addressed the frequency and possible effect of MASP2 polymorphisms in different populations or patients (Thiel et al, 2006(Thiel et al, , 2007(Thiel et al, , 2009Horcajada et al, 2009;Ramos-Casals et al, 2009;Vallès et al, 2009;Wang et al, 2009;Ytting et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Mannose‐binding lectin and MBL‐associated serine protease‐2 gene polymorphisms in a Brazilian population from Rio de Janeiro

Ferraroni

Segat

Guimarães

et al. 2011

Int J Immunogenetics

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Mannose-binding lectin (MBL) is a protein able to bind to carbohydrate patterns on pathogen membranes; upon MBL binding, its' associated serine protease MBL-associated serine protease type 2 (MASP2) is autoactivated, promoting the activation of complement via the lectin pathway. For both MBL2 and MASP2 genes, the frequencies of polymorphisms are extremely variable between different ethnicities, and this aspect has to be carefully considered when performing genetic studies. While polymorphisms in the MBL-encoding gene (MBL2) have been associated, depending upon ethnicity, with several diseases in different populations, little is known about the distribution of MASP2 gene polymorphisms in human populations. The aim of our study was thus to determine the frequencies of MBL2 (exon 1 and promoter) and MASP2 (p.D371Y) polymorphisms in a Brazilian population from Rio de Janeiro. A total of 294 blood donor samples were genotyped for 27 polymorphisms in the MBL2 gene by direct sequencing of a region spanning from the promoter polymorphism H/L rs11003125 to the rs1800451 polymorphism (at codon 57 in the first exon of the gene). Genotyping for MASP2 p.D371Y was carried out using fluorogenic probes. To our knowledge, this is the first study reporting the prevalence of the MASP2 p.D371Y polymorphism in a Brazilian population. The C allele frequency 39% is something intermediate between the reported 14% in Europeans and 90% in Sub-Saharan Africans. MBL2 polymorphisms frequencies were quite comparable to those previously reported for admixed Brazilians. Both MBL2 and MASP2 polymorphisms frequencies reported in our study for the admixed Brazilian population are somehow intermediate between those reported in Europeans and Africans, reflecting the ethnic composition of the southern Brazilian population, estimated to derive from an admixture of Caucasian (31%), African (34%) and Native American (33%) populations. In conclusion, our population genetic study describes the frequencies of MBL2 and MASP2 functional SNPs in a population from Rio de Janeiro, with the aim of adding new information concerning the distribution of these SNPs in a previously unanalysed Brazilian population, thus providing a new genetic tool for the evaluation of the association of MBL2 and MASP2 functional SNPs with diseases in Brazil, with particular emphasis on the state of Rio de Janeiro.

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“…RamosCasals et al suggested that in primary Sjogren syndrome patients, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage, since those with MBL-low genotypes have a less pronounced systemic and immunological disease expression than those carrying MBL-sufficient genotypes [100].…”

Section: The Complement System and Primary Sjögren's Syndromementioning

confidence: 99%

The complement system in systemic autoimmune disease

Chen

Daha

Kallenberg

2010

Journal of Autoimmunity

289

188

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Mannose-binding lectin-low genotypes are associated with milder systemic and immunological disease expression in primary Sjogren's syndrome

Abstract: SS patients with MBL-low genotypes have a less pronounced systemic and immunological disease expression in comparison with those carrying MBL-sufficient genotypes. In primary SS, MBL deficiency may represent a protective factor against the development of more aggressive autoimmune damage.

Cited by 20 publications

References 45 publications

Impaired Clearance of Early Apoptotic Cells Mediated by Inhibitory IgG Antibodies in Patients with Primary Sjögren's Syndrome

Impaired Clearance of Early Apoptotic Cells Mediated by Inhibitory IgG Antibodies in Patients with Primary Sjögren's Syndrome

Mannose‐binding lectin and MBL‐associated serine protease‐2 gene polymorphisms in a Brazilian population from Rio de Janeiro

The complement system in systemic autoimmune disease

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