Secretory Component Research Articles

Investigation of a monoclonal antibody against enterotoxigenic Escherichia coli, expressed as secretory IgA1 and IgA2 in plants

ABSTRACT Passive immunization with antibodies is a promising approach against enterotoxigenic Escherichia coli diarrhea, a prevalent disease in LMICs. The objective of this study was to investigate expression of a monoclonal anti-ETEC CfaE secretory IgA antibody in N. benthamiana plants, with a view to facilitating access to ETEC passive immunotherapy. SIgA1 and SIgA2 forms of mAb 68–81 were produced by co-expressing the light and engineered heavy chains with J chain and secretory component in N. benthamiana. Antibody expression and assembly were compared with CHO-derived antibodies by SDS-PAGE, western blotting, size-exclusion chromatography and LC-MS peptide mapping. N-linked glycosylation was assessed by rapid fluorescence/mass spectrometry and LC-ESI-MS. Susceptibility to gastric digestion was assessed in an in vitro model. Antibody function was compared for antigen binding, a Caco-2 cell-based ETEC adhesion assay, an ETEC hemagglutination inhibition assay and a murine in vivo challenge study. SIgA1 assembly appeared superior to SIgA2 in plants. Both sub-classes exhibited resistance to degradation by simulated gastric fluid, comparable to CHO-produced 68–61 SIgA1. The plant expressed SIgAs had more homogeneous N-glycosylation than CHO-derived SIgAs, but no alteration of in vitro functional activity was observed, including antibodies expressed in a plant line engineered for mammalian-like N glycosylation. The plant-derived SIgA2 mAb demonstrated protection against diarrhea in a murine infection model. Although antibody yield and purification need to be optimized, anti-ETEC SIgA antibodies produced in a low-cost plant platform are functionally equivalent to CHO antibodies, and provide promise for passive immunotherapy in LMICs.

The structures of secretory and dimeric immunoglobulin A.

Secretory (S) Immunoglobulin (Ig) A is the predominant mucosal antibody, which binds pathogens and commensal microbes. SIgA is a polymeric antibody, typically containing two copies of IgA that assemble with one joining-chain (JC) to form dimeric (d) IgA that is bound by the polymeric Ig-receptor ectodomain, called secretory component (SC). Here, we report the cryo-electron microscopy structures of murine SIgA and dIgA. Structures reveal two IgAs conjoined through four heavy-chain tailpieces and the JC that together form a β-sandwich-like fold. The two IgAs are bent and tilted with respect to each other, forming distinct concave and convex surfaces. In SIgA, SC is bound to one face, asymmetrically contacting both IgAs and JC. The bent and tilted arrangement of complex components limits the possible positions of both sets of antigen-binding fragments (Fabs) and preserves steric accessibility to receptor-binding sites, likely influencing antigen binding and effector functions.

Secretory IgA N-glycans contribute to the protection against E. coli O55 infection of germ-free piglets

Mucosal surfaces are colonized by highly diverse commensal microbiota. Coating with secretory IgA (SIgA) promotes the survival of commensal bacteria while it inhibits the invasion by pathogens. Bacterial coating could be mediated by antigen-specific SIgA recognition, polyreactivity, and/or by the SIgA-associated glycans. In contrast to many in vitro studies, only a few reported the effect of SIgA glycans in vivo. Here, we used a germ-free antibody-free newborn piglets model to compare the protective effect of SIgA, SIgA with enzymatically removed N-glycans, Fab, and Fc containing the secretory component (Fc-SC) during oral necrotoxigenic E. coli O55 challenge. SIgA, Fab, and Fc-SC were protective, whereas removal of N-glycans from SIgA reduced SIgA-mediated protection as demonstrated by piglets’ intestinal histology, clinical status, and survival. In vitro analyses indicated that deglycosylation of SIgA did not reduce agglutination of E. coli O55. These findings highlight the role of SIgA-associated N-glycans in protection. Further structural studies of SIgA-associated glycans would lead to the identification of those involved in the species-specific inhibition of attachment to corresponding epithelial cells.

FCRL4 Is an Fc Receptor for Systemic IgA, but Not Mucosal Secretory IgA.

Fc receptor-like (FCRL) 4 is an immunoregulatory receptor expressed on a subpopulation of human memory B cells of mucosa-associated lymphoid tissue. Fc receptor function of FCRL4 was demonstrated by binding of IgA to FCRL4 following heat aggregation of the Ig. In this study, we demonstrate that FCRL4 recognizes J chain-linked systemic IgA in the absence of heat aggregation. We further demonstrate that mucosal secretory IgA is not recognized by FCRL4 and that systemic IgA binding can be competitively inhibited by recombinant secretory component protein. Finally, we provide evidence that primary FCRL4-bearing human memory B cells are constitutively bound to IgA. Our study provides a mechanism for the negative regulatory activity of FCRL4 on AgR-mediated B cell activation.

P0724ASSOCIATIONS OF URINARY POLYMERIC IMMUNOGLOBULIN RECEPTOR PEPTIDES IN THE CONTEXT OF CARDIO-RENAL SYNDROM

Abstract Background and Aims The polymeric immunoglobulin receptor (pIgR) which transports immunoglobulins from the basolateral to the apical surface of epithelial cells was recently shown to be associated with kidney dysfunction. The immune defense is initiated at the apical surface where the N-terminal domain of pIgR, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to immunoglobulins. The aim of our study was to show the association of pIgR peptides with the cardio-renal syndrome in a large cohort and to get information on how the SC will be released. Method We investigated urinary peptides of 2707 individuals available in the Human Urine Proteome Database using capillary electrophoresis coupled to mass spectrometry. Results The mean abundance of 23 different pIgR peptides correlates negatively with the estimated glomerular filtration rate (eGFR, r=-0.314, p<0.0001). Furthermore, pIgR peptides are significantly increased in coronary artery disease after adjustment for eGFR. We further predicted the proteases involved in urinary peptide generation using the Proteasix tool. Peptide cleavage site analysis suggests that several, and not one, proteases are involved in the generation of the SC. Conclusion In this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and provide more detailed insights on how pIgR can be potentially cleaved to release the SC.

Longan Pulp Polysaccharide Protects Systemic Immunity and Intestinal Immunity in Mice Induced by Cyclophosphamide

Abstract Objectives This study aimed to explore the effect of longan pulp polysaccharide (LP) on the systemic immunity and intestinal mucosal immunity with immunosuppressive mice. The synthesis processing and secretion of intestinal secretory IgA (SIgA) were investigated. Methods Serum IgA, IgG, IgM and intestinal SIgA were detected by ELISA. Genes involved in the synthesis and secretion of SIgA were detected by Q-PCR and western blot. Results LP increased the thymus index, spleen index, and serum IgA level in cyclophosphamide (CTX)-treated mice. SIgA secretion in intestinal lumen was increased by LP as well. The underlying mechanism comes down to the facts as follows: LP increased intestinal cytokines expression and TGFβRII that is associated with pathways of IgA class switch recombination (CSR). By improving protein expression of mucosal address in cell-adhesion molecule-1 (MAdCAM-1) and integrin α4β7, LP was beneficial to gut homing of IgA + plasma cells. LP increased IgA, polymeric immunoglobulin receptor (pIgR), and secretory component (SC) to fortify the SIgA secretion. Conclusions This study suggested that moderate consumption of LP is helpful for improving systemic immunity and intestinal mucosal immunity via promotion of intestinal SIgA to strengthen the mucosal barrier. Funding Sources This work was supported by the National Key Research Project of China (2018YFC1602105, 2019YFD1002304), Guangdong Provincial Science and Technology Project (2018A050506050), President Foundation of Guangdong Academy of Agricultural Sciences (201812B).

Active free secretory component and secretory IgA in human milk: do maternal vaccination, allergy, infection, mode of delivery, nutrition and active lifestyle change their concentrations?

Free secretory component (free SC) in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion, but its concentration in human milk is unknown. To evaluate the relationship between free SC and SIgA, the influence of maternal factors (vaccination during pregnancy, allergy, previous infections, nutrition, mode of delivery and active lifestyle) on the concentrations of those secretory immune components in human milk was investigated. Concentration of active free SC and SIgA in 124 milk samples from 91 mothers were measured via ELISA. Free SC in milk from Tdap-vaccinated mothers was lower than the Tdap-flu-vaccinated, flu-vaccinated or Rhogam-vaccinated mothers. Free SC in mothers who had a cesarean delivery was higher than mothers who had a vaginal delivery. Free SC in the nonallergic group was higher than the allergic group. Free SC was higher in mothers who rarely/never eat junk food, than in mothers who always/frequently eat junk food. Free SC also was higher in the moderate exercise group (active lifestyle) compared with the group who rarely/never exercise (sedentary lifestyle). Free SC in human milk was not affected by previous maternal infection or probiotic supplementation whereas SIgA was not changed by all investigated maternal factors. This study suggests that active free SC is more impacted by maternal factors than active SIgA in human milk. Active free secretory component (free SC) is more impacted by maternal factors than active secretory IgA (SIgA) in human milk. Vaccination during pregnancy, allergy, nutrition, type of delivery and active lifestyle affect the secretion of free SC in human milk, but not SIgA secretion. Free SC in human milk is a critical constituent of secretory IgA (SIgA) for immune exclusion against pathogens and its active concentration in milk strongly varies between mothers, partially due to their specific maternal background.

Associations of urinary polymeric immunoglobulin receptor peptides in the context of cardio-renal syndrome

The polymeric immunoglobulin receptor (pIgR) transports immunoglobulins from the basolateral to the apical surface of epithelial cells. PIgR was recently shown to be associated with kidney dysfunction. The immune defense is initiated at the apical surface of epithelial cells where the N-terminal domain of pIgR, termed secretory component (SC), is proteolytically cleaved and released either unbound (free SC) or bound to immunoglobulins. The aim of our study was to evaluate the association of pIgR peptides with the cardio-renal syndrome in a large cohort and to obtain information on how the SC is released. We investigated urinary peptides of 2964 individuals available in the Human Urine Proteome Database generated using capillary electrophoresis coupled to mass spectrometry. The mean amplitude of 23 different pIgR peptides correlated negatively with the estimated glomerular filtration rate (eGFR, rho = −0.309, p < 0.0001). Furthermore, pIgR peptides were significantly increased in cardiovascular disease (coronary artery disease and heart failure) after adjustment for eGFR. We further predicted potential proteases involved in urinary peptide generation using the Proteasix algorithm. Peptide cleavage site analysis suggested that several, and not one, proteases are involved in the generation of the SC. In this large cohort, we could demonstrate that pIgR is associated with the cardio-renal syndrome and provided a more detailed insight on how pIgR can be potentially cleaved to release the SC.

Structural insights into secretory immunoglobulin A and its interaction with a pneumococcal adhesin.

Secretory Immunoglobulin A (SIgA) is the most abundant antibody at the mucosal surface. It possesses two additional subunits besides IgA: the joining chain (J-chain) and secretory component (SC). SC is the ectodomain of the polymeric immunoglobulin receptor (pIgR), which functions to transport IgA to the mucosa. How the J-chain and pIgR/SC facilitate the assembly and secretion of SIgA remains incompletely understood. Furthermore, during the infection of Streptococcus pneumoniae, the pneumococcal adhesin SpsA hijacks pIgR/SC and SIgA to gain entry to human cells and evade host defense. How SpsA targets pIgR/SC and SIgA also remains elusive. Here we report a cryo-electron microscopy structure of the Fc region of IgA1 (Fcα) in complex with the J-chain and SC (Fcα-J-SC), which reveals the organization principle of SIgA. We also present a structure of Fcα-J-SC complexed with SpsA, which uncovers the specific interactions between SpsA and human pIgR/SC. These results advance the molecular understanding of SIgA and shed light on S. pneumoniae pathogenesis.

Sequence characterization and N-glycoproteomics of secretory immunoglobulin A from donkey milk

Secretory immunoglobulin A (sIgA) is the major antibody present in the human milk where it confers passive immunity to neonates. Other than human, non-ruminants such as equine, swine etc., also possess sIgA in milk but detailed characterization is limited. In the present study, we characterized sIgA from donkey milk for amino acid sequence and N-glycosylation through LC-MS/MS analysis. The complete amino acid sequence of alpha chain constant region (CH) was elucidated. The sequence analysis of variable regions (VH and VL) and light chain constant region (CL) showed several amino acid substitutions indicating the presence of diverse immunoglobulin repertoire. Glycoproteomic analysis of secretory component revealed bi-antennary complex and hybrid types with differential core fucosylation at site N83LT, only complex glycans at N135GT, N423GT and N530LT with mainly NeuAc whereas N291QT harbors high mannose glycans. Heavy chain possesses majorly bi-antennary complex with differential core fucosylation at sites N139AS and N338VS, in which N338VS shows partial occupancy. Joining chain harbors only complex type at N72IS, with core fucosylation and terminal NeuGc to some extent. N-glycan repertoire in part is similar to human sIgA. This comprehensive analysis of sequence and glycan pattern of donkey milk sIgA would be beneficial for its potential applications.

Development of a rapid immunochromatographic strip test for the detection of porcine epidemic diarrhea virus specific SIgA in colostrum

Porcine epidemic diarrhea virus (PEDV) causes very high mortality in newborn piglets. The mucosal immune system in the gut must eliminate potential pathogens while maintaining a mutually beneficial relationship with the commensal microbiota. Antibodies derived from the secretory immunoglobulin A (SIgA) class, act as the first line of antigen-specific immunity in the gut by recognizing both pathogens and commensals. Therefore, the measurement of SIgA levels is an important index in evaluating PEDV infections and immune status. A simple and rapid method for the detection of PEDV-specific SIgA using an immunochromatographic test strip has been developed; incorporating a colloidal gold-labeled anti-SIgA secretory component (SC) mAb probe for the detection of anti-PEDV-specific SIgA in swine. On the strip, a gold-labeled anti-SIgA SC mAb was applied to a conjugate pad; purified PEDV particles and goat anti-mouse antibodies were blotted onto a nitrocellulose membrane to form the test and control lines, respectively. Results showed that the immunochromatographic test strip had high sensitivity and specificity. When compared with enzyme-linked immunosorbent assay, kappa value suggesting that the strip could be used to detect PEDV specific SIgA in colostrum samples. Furthermore, the strip assay is rapid and easy to perform with no requirement for professional-level skills or equipment. We found that the immunochromatographic test strip was a rapid, sensitive, and reliable method for the identification of PEDV specific SIgA, indicating its suitability for epidemiological surveillance as well as vaccine immunity when studying PEDV.

Hefty structures of IgA and IgM complexes

Immunology Immunoglobulin M (IgM) and IgA are antibody isotypes that can form higher-order secretory complexes (sIgM and sIgA), which allows them to effectively bind and neutralize antigens with low-affinity repetitive epitopes, such as those found on the surface of many bacteria and viruses. The assembly and transport of these molecules is also dependent on the joining chain (J-chain) and the polymeric immunoglobulin receptor (pIgR) secretory component (SC). The architecture of these complex, multimeric structures has remained elusive. Li et al. resolved cryo–electron microscopy structures of the sIgM-Fc pentamer in complex with the J-chain and SC. Using similar techniques, Kumar et al. visualized dimeric, tetrameric, and pentameric structures of secretory sIgA-Fc interacting with the J-chain and SC. Both groups report highly similar mechanisms wherein the J-chain serves as a template for antibody oligomerization. An unanticipated, amyloid-like assembly of the oligomerized structure is present in both cases, with the J-chain conferring asymmetry for pIgR binding and transcytosis. These studies may inform structure-based engineering of these molecules for future therapeutic purposes. Science , this issue p. [1014][1], p. [1008][2] [1]: /lookup/doi/10.1126/science.aaz5425 [2]: /lookup/doi/10.1126/science.aaz5807

Structure of the secretory immunoglobulin A core.

Secretory immunoglobulin A (sIgA) represents the immune system's first line of defense against mucosal pathogens. IgAs are transported across the epithelium, as dimers and higher-order polymers, by the polymeric immunoglobulin receptor (pIgR). Upon reaching the luminal side, sIgAs mediate host protection and pathogen neutralization. In recent years, an increasing amount of attention has been given to IgA as a novel therapeutic antibody. However, despite extensive studies, sIgA structures have remained elusive. Here, we determine the atomic resolution structures of dimeric, tetrameric, and pentameric IgA-Fc linked by the joining chain (JC) and in complex with the secretory component of the pIgR. We suggest a mechanism in which the JC templates IgA oligomerization and imparts asymmetry for pIgR binding and transcytosis. This framework will inform the design of future IgA-based therapeutics.

The Effects of Secretory IgA in the Mucosal Immune System.

Immunoglobulin A (IgA) is the most abundant antibody isotype in the mucosal immune system. Structurally, IgA in the mucosal surface is a polymeric structure, while serum IgA is monomeric. Secretory IgA (sIgA) is one of the polymeric IgAs composed of dimeric IgA, J chain, and secretory component (SC). Most of sIgAs were generated by gut and have effects in situ. Besides the function of “immune exclusion,” a nonspecific immune role, recent studies found it also played an important role in the specific immunity and immunoregulation. Thanks to the critical role of sIgA during the mucosal immune system homeostasis between commensal microorganisms and pathogens; it has been an important field exploring the relationship between sIgA and commensal microorganisms.

Effects of Milk Secretory Immunoglobulin A on the Commensal Microbiota.

Secretory immunoglobulin A (SIgA) is intimately involved in the transfer of maternal immunity to the newborn breastfed infant. Recent research demonstrates the significance of SIgA in the initial development of the newborn's microbiota and in the establishment of a tolerogenic immunologic disposition towards nonpathogenic organisms and environmental antigens. SIgA has long been known to prevent pathogen binding to the host epithelium through immune exclusion involving numerous mechanisms. This process primarily involves T-cell-dependent, somatically hypermutated monoclonal antibodies with high specificity towards pathogen surface antigens, and the success of the immune response is dependent upon the specific antigen recognition. Whereas this role is important, there is an alternate, dual role for SIgA in the health of the host - protection and promotion of commensal colonization and maintenance of homeostatic immunity. This latter role is primarily dependent upon N- and O-glycan moieties lining the secretory component and heavy chain of the SIgA dimer, with interactions independent of immunoglobulin specificity. These SIgA molecules are nonspecific polyclonal antibodies generated from plasma cells activated by dendritic cell sampling of luminal contents in the absence of inflammation. Breast milk is the primary supply of such polyclonal polyreactive SIgA in the initial stages of neonatal colonization, and it provides vital pathogen resistance while promoting colonization of commensal microbiota.

Increased Glomerular Hydrostatic Pressure is Associated with Tubular Creatinine Reabsorption in Healthy Subjects

Background: Cr is secreted by the proximal tubules and thus Cr clearance (C_cr) can overestimate inulin clearance (C_in). However, in some cases, C_cr can even underestimate C_in. This suggests that Cr could be reabsorbed in the tubuli. We examined the clinical parameters that are associated with tubular Cr reabsorption. Methods: In 80 kidney donor candidates (53.9 ± 13.2 years, 29 males), C_in and para-aminohippuric acid clearance were measured simultaneously. Intrarenal hemodynamic parameters were calculated by Gomez’s formulae. To quantify the secretory component of C_cr (SF_cr), it was calculated as follows: SF_cr = (C_cr − C_in)/C_cr. Results: Twenty-five subjects (31.3%) showed SF_cr values <0. SF_cr that correlated significantly and negatively with efferent arteriolar resistance (R_e) and glomerular hydrostatic pressure (P_glo) (R_e: r = −0.30, p = 0.008; P_glo: r = −0.28, p = 0.025). In multiple regression analyses, R_e and P_glo were significantly and negatively associated with SF_cr after adjustment for other confounders. Conclusions: These findings suggest that tubular reabsorption of Cr can occur in some cases. Intrarenal glomerular hemodynamic burden may be related to tubular creatinine reabsorption, which possibly leads to lower C_cr values.

Moderate hyperoxia plays a protective role in lung bronchial epithelial cells.

Oxygen therapy is commonly used in clinical settings, but several problems may result from improper use. Oxygen poisoning involves the initiation of a series of inflammatory reactions. In this study, we compared the effects of moderate hyperoxia (40% O2) and extreme hyperoxia (85% O2) on pulmonary bronchial epithelial cells. Normal human tracheobronchial epithelium (NHBE) cells were exposed to hyperoxia (40% and 85%) for 24 hours, and their survival rates were determined by the colorimetic assay, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5- diphenyltetrazolium bromide). The protein and mRNA levels of RelA, RelB, ASK1, TNF-α and secretory component (SC) were detected by immunohistochemical staining, western blot, and real-time polymerase chain reaction. The NHBE cell survival increased in the presence of moderate hyperoxia. RelA, RelB, ASK1, TNF-α and SC expressions were significantly higher in the 85% O2 group in comparison with the control group and the 40% O2 group. In the 40% O2 group, RelA, RelB, ASK1 and TNF-α were upregulated, but SC expression was not significantly different than that of the control group. However, compared with the 85% O2 group, SC expression was significantly lower in the 40% O2 group. These results suggest that moderate hyperoxia promotes proliferation in NHBE cells and activates TNF-α and downstream ASK1. Then TNF-α activates NF-κB and SC to play a protective role.

THE STATE OF THE MUCOSAL IMMUNITY OF THE ROGENITAL TRACT IN PATIENTS WITH VARIOUS VARIANTS OF CLINICAL COURSE OF ACUTE UNCOMPLICATED PYELONEPHRITIS

The purpose of the work was to investigate the state of mucosal immunity of the urinary and genital tract in patients with acute uncomplicated pyelonephritis (AUP), depending on the severity of the disease.&#x0D; Methods. 124 women with AUP and with concomitant chronic inflammatory diseases of the pelvic organs (CIDPO) and 23 clinically healthy women were examined. To assess the clinical picture of AUP was used a division into 3 variants of the clinical course (VCC): mild (n = 105), moderate severity (n = 90) and severe (n = 51). Humoral indicators of mucosal immunity were determined in 64 urine samples and 121 vaginal washings by enzymelinked immunosorbent assay. The levels of immunoglobulins (Ig) A, M, G, secretory IgA (sIgA), lactoferrin (LF) myeloperoxidase (MPO) and lysozyme, C3-component of complement (C3), secretory component, tumor necrosis factor-α (TNF-α) were determined. The concentration of β -defensin-2 was determined in vaginal washings, and the levels of interleukins 10 and 15 – in urine.&#x0D; Results. A significant increase of the concentration of C3, LF, lysozyme, MPO, sIgA, and TNF-α relative to their reference values was found in the urine of patients with different variants of clinical course of AUP. The smallest median values for LF, lysozyme and MPO were recorded in patients with severe VCC AUP. An increase of TNF-α level was more characteristic for patients with moderate severity and severe VCT. The highest increase of IgA, IgM, IgG levels was found in patients with mild VCT. Significantly elevated levels of MPO, IgA, IgG and TNF-α were detected in vaginal washings in women of all groups relative to reference indicators. The highest (p&lt;0.05) increase in the level of non-specific immunity factors (lysozyme and MPO) was observed in vaginal washings in patients with severe VCT, and specific (IgA, IgM and IgG) – in patients with mild VCT.&#x0D; Conclusions. In patients with various clinical course of AUP, a significant increase of the humoral factors of nonspecific and specific immunity and cytokines in urine was established relative to reference indicators; to a lesser extent for non-specific indicators of immunity and to a greater extent for TNF-α in patients with severe VCT. Concomitant CIDPO contributed to the greatest increase in washings of MPO and lysozyme levels in patients with severe VCT, and the level of immunoglobulins of all classes – in patients with mild.

Purification and Characterisation of Badger IgA and Its Detection in the Context of Tuberculosis.

European badgers are a wildlife reservoir of bovine tuberculosis in parts of Great Britain. Accurate diagnosis of tuberculosis in badgers is important for the development of strategies for the control of the disease. Sensitive serological tests for badger TB are needed for reasons such as cost and simplicity. Assay of mucosal IgA could be useful for diagnosing respiratory pathogens such as Mycobacterium bovis and for monitoring the response to mucosal vaccination. To develop an IgA assay, we purified secretory IgA from badger bile, identifying secretory component (SC), heavy chain (HC) and light chain (LC), at 66, 46 and 27 Kda, respectively, on the basis of size comparison with other species. Monoclonal antibodies (mAbs) were generated to purified IgA. We selected two for ELISA development. The detection limit of the IgA-specific mAbs was found to be approximately 20 ng/mL when titrated against purified badger bile. One monoclonal antibody specific for badger IgA was used to detect IgA in serum and tracheal aspirate with specificity to an immunodominant antigen of M. bovis. An M. bovis infection dose-dependent IgA response was observed in experimentally infected badgers. IgA was also detected by immunohistochemistry in the lungs of bTB-infected badgers. With further characterisation, these represent new reagents for the study of the IgA response in badgers.

Elevated free secretory component in early rheumatoid arthritis and prior to arthritis development in patients at increased risk.

ObjectivesConsidering growing evidence of mucosal involvement in RA induction, this study investigated circulating free secretory component (SC) in patients with either recent-onset RA or with ACPA and musculoskeletal pain.MethodsTwo prospective cohorts were studied: TIRA-2 comprising 452 recent-onset RA patients with 3 years of clinical and radiological follow-up, and TIRx patients (n = 104) with ACPA IgG and musculoskeletal pain followed for 290 weeks (median). Blood donors and three different chronic inflammatory diseases served as controls. Free SC was analysed by sandwich ELISA.ResultsSerum levels of free SC were significantly higher in TIRA-2 patients compared with TIRx and all control groups (P < 0.01). Among TIRx patients who subsequently developed arthritis, free SC levels were higher compared with all control groups (P < 0.05) except ankylosing spondylitis (P = 0.74). In TIRA-2, patients with ACPA had higher baseline levels of free SC compared with ACPA negative patients (P < 0.001). Free SC status at baseline did not predict radiographic joint damage or disease activity over time. In TIRx, elevated free SC at baseline trendwise associated with arthritis development during follow-up (P = 0.066) but this disappeared when adjusting for confounders (P = 0.72). Cigarette smoking was associated with higher levels of free SC in both cohorts.ConclusionSerum free SC levels are increased in recent-onset RA compared with other inflammatory diseases, and associate with ACPA and smoking. Free SC is elevated before arthritis development among ACPA positive patients with musculoskeletal pain, but does not predict arthritis development. These findings support mucosal engagement in RA development.