Propensity of IgA to self-aggregate via tailpiece cysteine-471 and treatment of IgA nephropathy using cysteamine.

IgA nephropathy is caused by deposition of circulatory IgA1 in the kidney. Hypogalactosylated IgA1 has the propensity to form poly-IgA aggregates that are prone to deposition. Herein, we purified poly-IgA from the plasma of patients with IgA nephropathy and showed that the complex is susceptible to reducing conditions, suggesting intermolecular disulfide connections between IgA units. We sought to find the cysteine residue(s) that form intermolecular disulfide. Naturally assembled dimeric IgA, also known as secretory IgA, involves a J chain subunit connected with 2 IgA1 molecules via their penultimate cysteine-471 residue on a "tailpiece" segment of IgA heavy chain. It is plausible that, with the absence of J chain, the cysteine residue of mono-IgA1 might aberrantly form a disulfide bond in poly-IgA formation. Mutagenesis confirmed that cysteine-471 is capable of promoting IgA aggregation. These discoveries prompted us to test thiol-based drugs for stabilizing cysteine. Specifically, the cystine-reducing drug cysteamine used for treatment of cystinosis showed a remarkable potency in preventing self-aggregation of IgA. When administrated to rat and mouse models of IgA nephropathy, cysteamine significantly reduced glomerular IgA deposition. Collectively, our results reveal a potentially novel molecular mechanism for aberrant formation of IgA aggregates, to which the repurposed cystinosis drug cysteamine was efficacious in preventing renal IgA deposition.

Enzymatically synthesized exopolysaccharide of a probiotic strain Leuconostoc mesenteroides NTM048 shows adjuvant activity to promote IgA antibody responses.

Leuconostoc mesenteroides strain NTM048 produces an exopolysaccharide (EPS; glucose polymers 94% and fructose polymers 6%) with adjuvanticity for mucosal vaccination. Strain NTM048 includes three putative EPS-synthesizing genes, gtf1 and gtf2 for synthesizing glucose polymers, and lvnS for synthesizing fructose polymer. To elucidate the key polymer structure for adjuvanticity, two genes, gtf1 and gtf2, which were annotated as glycoside hydrolase family 70 enzyme genes, were expressed in Escherichia coli. Glycosyl-linkage composition analysis and NMR analysis showed that the recombinant enzyme Gtf1 produced a soluble form of α-1,6-glucan, whereas the recombinant enzyme Gtf2 produced glucans with approximately equal percentages of α-1,6- and α-1,3-glucose residues both in the supernatant (S-glucan) and as a precipitate (P-glucan). Comparison of polysaccharides synthesized by Gtf1, Gtf2, and LvnS revealed that Gtf2-S-glucan, which was produced in the supernatant by Gtf2 and formed particles of 7.8 µm, possessed 1.8-fold higher ability to stimulate IgA production from murine Peyer's patch cells than native NTM048 EPS. Evaluation of adjuvanticity by intranasal administration of mice with an antigen (ovalbumin) and Gtf2-S-glucan or NTM048 EPS showed that Gtf2-S-glucan induced the production of higher antigen-specific antibodies in the airway mucosa and plasma, suggesting a pivotal role of Gtf2-S-glucan in the adjuvanticity of NTM048 EPS.

Dysregulation of murine immune functions on inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole, or propionic acid.

Animal husbandry workers are exposed to various malodorous compounds in the workplace. Although these compounds cause severe nuisance, no systemic investigation of their effects on the immune system has been conducted. To address this issue, we evaluated the effects of inhalational exposure to ammonia, dimethyl disulfide, 3-methylindole (3-MI), and propionic acid (PA), representing four major groups of malodorous compounds, on humoral and cellular immunity in mice. Mice were exposed to the substances (low dose: 10 µL and high dose: 200 µL) for 10 min/day for 4 weeks in a modified standard mouse cage. Neutrophil% and splenic cytotoxic T cell% were significantly lower in the high-dose ammonia group than in the vehicle control. Exposure to ammonia and 3-MI increased immature thymic T lymphocyte% relative to control and concomitantly decreased both mature helper and cytotoxic T-cell populations in the thymus. In the ammonia exposure group, levels of serum immunoglobulin E and immunoglobulin A were elevated, and the IgG2a:IgG1 ratio in the serum was reduced in a dose-dependent manner. Splenic natural killer cell activity was significantly less in the PA exposure group than in the control. Overall, our findings suggest that inhalational exposure to these malodorous substances disturbs immune homeostasis in vivo.

Immunomodulatory Effect of a Salvia plebeia R. Aqueous Extract in Forced Swimming Exercise-induced Mice.

This study investigated the immunomodulatory effect of Salvia plebeia R. aqueous extract (FIE-SP, SPW) in forced swimming exercise-induced mice and the immunostimulatory effects on Raw264.7 cells. Mice were randomly assigned to four groups: the control group (CON), the forced swimming test group (FST), and two FIE-SP groups (low and high dose of FIE-SP). Compared with the control group, the FIE-SP groups showed significantly increased ratios of T lymphocyte surface markers CD4+/CD8+ and major histocompatibility complex (MHC)I/MHCII, as well as increased concentrations of immunoglobulin (Ig)A and IgG. FIE-SP groups significantly increased Th1 cytokines and decreased Th2 cytokines compared with negative control exercise-induced mice. Conversely, the immunostimulatory effects of FIE-SP significantly increased phagocytic activities, nitric oxide (NO) production, and pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin (IL)-1ß in Raw264.7 cells. Furthermore, FIE-SP increased natural killer (NK) cell activities and cytokines (IL-12) in splenocytes compared with the CON group. These results indicated that FIE-SP supplementation could prevent imbalanced immune states and produce immunostimulatory effects to support innate immunity.

A case of proliferative glomerulonephritis with immunoglobulin A1-lambda deposits successfully treated by chemotherapy.

A 74-year-old man presented with nephrotic syndrome and kidney insufficiency. Laboratory tests revealed monoclonal gammopathy of immunoglobulin A-lambda. Renal biopsy revealed diffuse mesangial proliferation and double-contoured basement membranes. Immunofluorescent analyses showed granular deposition of immunoglobulin A and C3 at the capillary walls and mesangial regions. Immunohistochemistry suggested monoclonal deposition of immunoglobulin A1-lambda. Electron microscopic analyses showed finely granular electron-dense deposits at mesangial and subendothelial areas. These findings suggested immunoglobulin A-type proliferative glomerulonephritis with monoclonal immunoglobulin deposits. Based on the results of bone marrow aspiration, multiple myeloma was diagnosed. Because the renal manifestation was considered to be affected by monoclonal gammopathy, chemotherapy was initiated rather than immunomodulatory therapy. Although bortezomib and dexamethasone proved ineffective, second chemotherapy with elotuzumab, lenalidomide, and dexamethasone was successful, and kidney function recovered. Effective treatments for proliferative glomerulonephritis with monoclonal immunoglobulin deposits have not been established. This represents the first description of a patient successfully treated for proliferative glomerulonephritis with monoclonal immunoglobulin deposits by chemotherapy using elotuzumab.

Triptolide inhibits tonsillar IgA production by upregulating FDC-SP in IgA nephropathy.

IgA nephropathy (IgAN) is primarily resulted of qualitative abnormality of IgA. The occurrence of IgAN is associated with affected tonsils which enhances the IgA production via IgA class switching and immuno-activation. Follicular dendritic cell-secreted protein (FDC-SP) was found to be a negative effect for IgA production in tonsil. The previous studies suggested that Triptolide might reduce IgA production by its immunosuppression role. Given this background, this study investigated the mechanisms underlying the role of Triptolide and FDC-SP in the generation of IgA and IgA class switching in tonsil of IgAN patients. Immunohistochemistry and reverse transcription-polymerase chain reaction revealed that the expression of FDC-SP was increased in the tonsils of IgAN patients with Triptolide treatment compared with those without treatment. Meanwhile, the expression of FDC-SP was negatively correlated with IgA inducing cytokines in the tonsils of IgAN patients treated with Triptolide, due to the significant decreased IgA-bearing cells. The expression of FDC-SP in tonsillar tissue was confirmed by double immunofluorescence. Importantly, Triptolide promoted FDC-SP secretion, and correlated negatively with decreased IgA production in isolated FDC-associated clusters, which had been isolated from patients without TW treatment previously. Our study demonstrated that Triptolide might have an impact on FDC-SP production and downregulation of IgA synthesis in the tonsils of IgAN patients, which could be a promising strategy for therapeutic intervention in IgAN patients.

Alemtuzumab therapy changes immunoglobulin levels in peripheral blood and CSF.

OBJECTIVE: The use of alemtuzumab, a humanized monoclonal anti-CD52 antibody has changed the therapy of highly active relapsing-remitting MS (RRMS). Alemtuzumab infusion depletes most lymphocytes in peripheral blood, whereas differential recovery of immune cells, probably those with a less CNS-autoreactive phenotype, is supposed to underlie its long-lasting effects. To determine whether alemtuzumab significantly reduces immunoglobulin levels in blood and CSF of treated patients, we analyzed blood and CSF samples of 38 patients with MS treated with alemtuzumab regarding changes in immunoglobulin levels. METHODS: Blood and CSF samples of patients were collected at the beginning of alemtuzumab treatment and at 12, 24, and 36 months after the first administration of the drug. Specimens were analyzed regarding immunoglobulin concentrations in blood and CSF. RESULTS: We observed significant and dose-dependent reductions of immunoglobulin levels (IgG, IgM, and IgA) in serum and CSF 12 and 24 months following 2 courses of alemtuzumab. Patients with persistent or returning disease activity who were treated with a third course of alemtuzumab exhibited even further decrease in IgG levels compared with matched controls treated twice. Here, alemtuzumab-treated patients with IgG levels below the lower limits of normal were more susceptible to pneumonia, sinusitis, and otitis, whereas upper respiratory tract and urinary tract infections were not associated therewith. CONCLUSIONS: Our results suggest to monitor IgG levels for safety reasons in patients treated with alemtuzumab-in particular when additional treatment courses are required-and to consider preventive action in critical cases. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with RRMS alemtuzumab reduces immunoglobulin levels.

Bevacizumab-induced immunoglobulin A vasculitis with nephritis: A case report.

RATIONALE: Bevacizumab-an inhibitor of vascular endothelial growth factor-is effective against various advanced cancers. However, it is associated with the development of hypertension and high-grade proteinuria during thrombotic microangiopathy of the kidney. In addition, there are several reports of immunoglobulin A deposition in the glomeruli, but the etiology is unclear. PATIENT CONCERNS: A 67-year-old Japanese man with metastatic rectal cancer underwent low anterior rectal resection, followed by treatment with bevacizumab and SOX (S-1 plus oxaliplatin). Six months later, the patient developed hematuria, nephrotic syndrome, and purpura. DIAGNOSES: Renal biopsy revealed endocapillary proliferative glomerulonephritis. Immunofluorescence analyses showed granular mesangial deposition of galactose-deficient immunoglobulin A1. Skin biopsy revealed leukocytoclastic vasculitis. INTERVENTIONS: We ceased bevacizumab treatment, while continuing the remaining chemotherapy regimen, as we suspected bevacizumab-induced nephropathy. OUTCOMES: Proteinuria and purpura improved immediately after cessation of bevacizumab. We identified this as a case of bevacizumab-induced immunoglobulin A vasculitis with nephritis. LESSONS: To our knowledge, this is the first case of bevacizumab-related immunoglobulin A vasculitis with nephritis, as evidenced by galactose-deficient immunoglobulin A1. When a patient's urine tests are abnormal during bevacizumab treatment, clinicians should consider not only thrombotic microangiopathy but also vasculitis.

Non-invasive quantification of immunoglobulin A in chimpanzees (Pan troglodytes schweinfurthii) at Gombe National Park, Tanzania.

Immunoglobulin A (IgA) is the primary antibody responsible for mucosal defense in mammals and has been used as a marker for chronic stress and immune status. Therefore, this antibody may provide a more reliable indicator of an individual's immunocompetence than is currently available through other methods. Immunoglobulin A has never before been quantified in a wild population of non-human primates using non-invasive sample collection techniques. In this study, we present methodology for non-invasive IgA extraction in the field and provide quantification of mean fecal IgA concentrations in wild chimpanzees (Pan troglodytes schweinfurthii). During the study period (November 2009-October 2010), we collected fecal samples (N = 1463) from 59 individuals at Gombe National Park, Tanzania. We modified a field extraction technique for steroidal hormones to extract IgA from the fecal samples and then quantified mean IgA concentrations (ng/g) using a commercial human IgA enzyme immunoassay. Mean IgA concentration varied among individuals but not by sex or reproductive status. Mature animals tended toward higher mean IgA concentration than immature. Mean IgA concentration differed by quartile season, following a similar pattern previously observed for respiratory illness rates in this population, with the late dry season having significantly higher averages than the late wet. A circadian rhythm was also evident with mean IgA concentrations higher in samples collected in the latter half of the day. These demographic and temporal patterns of IgA concentration provide baseline values necessary to interpret future results, which may be combined with other health values to better understand the role of health and long-term stress in wild great ape populations. Am. J. Primatol. 80:e22558, 2018. © 2016 Wiley Periodicals, Inc.

Sodium fluoride (NaF) causes toxic effects on splenic development in mice.

At present, very limited studies focus on the toxic effect of sodium fluoride (NaF) on splenic development of human and animals in vivo. This study was firstly designed to evaluate the toxic effects of NaF on the splenic development of mice in vivo by observing histopathological lesions, changes of splenic growth index (GI), T and B cells, immunoglobulin A (IgA), immunoglobulin G (IgG) and immunoglobulin M (IgM) contents, cytokine protein expression levels, and cell cycle and cyclins/cdks protein expression levels using the methods of pathology, flow cytometry (FCM), western blot (WB), and enzyme-linked immunosorbent assay (ELISA). A total of 240 ICR mice were equally allocated into four groups with intragastric administration of distilled water in the control group and 12, 24, 48 mg/kg NaF solution in the experimental groups for 42 days. The results showed that NaF in 12 mg/kg and over caused the toxic effects on splenic development, which was characterized by reducing growth index and lymphocytes in the white and red pulp histopathologically, increasing cell percentages of the G0/G1 phase and decreasing cell percentages of the S phase, and reducing T cells and B cells as well as IgA, IgG, and IgM contents when compared with those in the control group. Concurrently, cytokines including interleukin-2 (IL-2), transforming growth factor beta (TGF-ß), tumor necrosis factor alpha (TNF-α), interferon gamma (IFN-γ) and cyclin (E/D and CDK2/4) protein expression levels were markedly decreased (P < 0.05 or P < 0.01), and interleukin-10 (IL-10) protein expression levels were significantly increased (P < 0.05 and P < 0.01) in the three NaF-treated groups. Toxic effects finally impaired the splenic cellular immunity and humoral immunity due to the reduction of T and B cell population and activity. Cell cycle arrest is the molecular basis of NaF-caused toxic effects on the splenic development.

S-1-Propenylcysteine promotes the differentiation of B cells into IgA-producing cells by the induction of Erk1/2-dependent Xbp1 expression in Peyer's patches.

OBJECTIVES: S-Allylcysteine (SAC) and S-1-propenylcysteine (S1PC) are the characteristic sulfur-containing amino acids in aged garlic extract. In this study, we investigated the effect of SAC and S1PC on intestinal immunoglobulin (Ig)A production to gain insight into the immunomodulatory effect of aged garlic extract. METHODS: In vitro study: Mouse splenic lymphocytes were treated with S1PC (0.1 and 0.3 mM) or SAC (0.1 and 0.3 mM) for 3 d, and IgA concentration in the culture medium was examined. In vivo study: Mice were orally administrated S1PC (7.5, 15, and 30 mg/kg) for 5 d and the IgA level in the intestinal lavage fluids as well as the population of IgA-producing cells in Peyer's patches were measured using mouse IgA enzyme-linked immunosorbent assay quantification set and flow cytometer, respectively. RESULTS: S1PC enhanced IgA production in mouse splenic lymphocytes in culture. However, SAC was ineffective. In addition, oral administration of S1PC to mice increased the IgA level and number of IgA-producing cells in Peyer's Patches. Furthermore, S1PC induced the expression of X-box binding protein 1 (Xbp1) mRNA, an inducer of plasma cell differentiation, in Peyer's patches. This induction was accompanied by the degradation of paired box protein 5 and the activation of mitogen activated protein/extracellular signal-regulated kinase signaling pathway. CONCLUSION: These results suggest that S1PC increases IgA-producing cells via the enhancement of Erk1/2-mediated Xbp1 expression in the intestine.

IgA1 Protease Treatment Reverses Mesangial Deposits and Hematuria in a Model of IgA Nephropathy.

IgA nephropathy (IgAN), characterized by mesangial IgA1 deposits, is a leading cause of renal failure worldwide. IgAN pathogenesis involves circulating hypogalactosylated IgA1 complexed with soluble IgA Fc receptor I (sCD89) and/or anti-hypogalactosylated-IgA1 autoantibodies, but no specific treatment is available for IgAN. The absence of IgA1 and CD89 homologs in the mouse has precluded in vivo proof-of-concept studies of specific therapies targeting IgA1. However, the α1KI­CD89Tg mouse model of IgAN, which expresses human IgA1 and human CD89, allows in vivo testing of recombinant IgA1 protease (IgA1­P), a bacterial protein that selectively cleaves human IgA1. Mice injected with IgA1­P (1-10 mg/kg) had Fc fragments of IgA1 in both serum and urine, associated with a decrease in IgA1-sCD89 complexes. Levels of mesangial IgA1 deposits and the binding partners of these deposits (sCD89, transferrin receptor, and transglutaminase 2) decreased markedly 1 week after treatment, as did the levels of C3 deposition, CD11b(+) infiltrating cells, and fibronectin. Antiprotease antibodies did not significantly alter IgA1­P activity. Moreover, hematuria consistently decreased after treatment. In conclusion, IgA1­P strongly diminishes human IgA1 mesangial deposits and reduces inflammation, fibrosis, and hematuria in a mouse IgAN model, and therefore may be a plausible treatment for patients with IgAN.

Catalytic autoantibodies against myelin basic protein (MBP) isolated from serum of autistic children impair in vitro models of synaptic plasticity in rat hippocampus.

Autoantibodies from autistic spectrum disorder (ASD) patients react with multiple proteins expressed in the brain. One such autoantibody targets myelin basic protein (MBP). ASD patients have autoantibodies to MBP of both the IgG and IgA classes in high titers, but no autoantibodies of the IgM class. IgA autoantibodies act as serine proteinases and degrade MBP in vitro. They also induce a decrease in long-term potentiation in the hippocampi of rats either perfused with or previously inoculated with this IgA. Because this class of autoantibody causes myelin sheath destruction in multiple sclerosis (MS), we hypothesized a similar pathological role for them in ASD.

Transcutaneous immunization with phosphorylcholine induces antigen-specific mucosal and systemic immune responses in BALB/c mice.

OBJECTIVE: Transcutaneous immunization (TCI) is a novel route of vaccination through application of a topical vaccine antigen on the skin. Phosphorylcholine (PC) is a structural component of a variety of pathogens and anti-PC immune responses protect mice against invasive bacterial diseases. The purpose of the study was to examine the effect of TCI using PC in BALB/c mice. METHODS: TCI was performed in BALB/c mice using PC-keyhole limpet hemocyanin (KLH) plus cholera toxin (CT). Immunogenicity was evaluated by measuring PC-specific IgG and specific IgG1, IgG2a, IgM, IgA, and secretory IgA antibodies by ELISA. The concentrations of IL-4, IL-5, IL-10, IL-12, IL-13 and IFN-γ were also measured using ELISA for mouse. RESULTS: Six months after immunization, IgG after TCI using PC plus CT was significantly higher than in controls, but this was not found for IgA. In saliva, secretory IgA antibodies decreased with a peak level at 2-3 months. IgG1 was significantly higher than IgG2 after TCI. Production of IL-4 from CD4(+) cells was significantly higher after TCI than in controls, whereas production of IFN-γ, IL-5, IL-12 and IL-13 was not detected in either group. CONCLUSION: These results suggest that TCI using PC plus CT with BALB/c mice is a simple approach for induction of systemic and mucosal immune responses that are shifted in the Th-2 direction.

Estrogen modulation of pneumonia? An immunoglobulin A effect.

BACKGROUND: Laboratory and clinical studies demonstrated a salutary effect of estradiol (E2) on pneumonia and other infectious complications after trauma, while dihydrotestosterone (DHT) failed to show a similar effect. Secretory immunoglobulin A is the principle antibody in the respiratory and other mucosal secretions. Immunoglobulin A (IgA) production and transport into the mucosal secretion is regulated by Toll-like receptor 4 (TLR-4). In addition, E2 may influence immune regulatory cells via TLR-4. We hypothesized that the protective effect of E2 on the development of pneumonia may be related to modulation of IgA transport into respiratory secretions. METHODS: Calu-3 respiratory epithelial cell monolayers were established in a two-chamber cell culture system. Calu-3 cells were then treated with either E2 or DHT for 3 days for maximal cell stimulation. Dimeric IgA was added to the basal chamber of Calu-3 cells, and IgA transcellular transport was indexed by recovery of secretory immunoglobulin A in the apical chamber media. In separate experiments, Klebsiella pneumonia (10(5) CFU/mL) was added to the apical chamber of treated Calu-3 cell monolayers, and bacterial passage across Calu-3 cells was determined by bacterial recovery from the basal chamber. Calu-3 cells not treated with E2 or DHT served as control. RESULTS: Calu-3 cells pretreated with E2 significantly increased IgA transport, and this effect was augmented in a dose-dependent fashion. Only cells pretreated with E2 significantly decreased bacterial passage, and this effect was exhibited in a dose- and time-dependent fashion. E2 led to a significant increase in TLR-4 expression. CONCLUSION: The protective effect of E2 against pneumonia may be related to augmented transport of IgA into the respiratory mucosal secretions.

Management of linear IgA disease.

Linear immunoglobulin A (IgA) disease is an acquired autoimmune blistering disease of the skin and mucous membranes that runs a chronic course over 3 to 6 years before remitting. It typically presents with papulovesicles and blisters configured in an arcuate pattern on an urticated base, with 2 peaks of onset. The first peak is in young prepubescent children, called chronic bullous disease of childhood, and the second peak affects patients older than 60 years of age. In this article, the management of linear IgA in adults is considered.

Immunomodulatory agents against IgA nephropathy.

Synthesis of aberrant IgA molecules as the key pathogenetic mechanism of immunoglobulin A nephropathy (IgAN) apparently forms a potential scientific rationale for applying immunomodulatory agents in the treatment of IgAN. There is evidence that corticosteroids can steadily reduce proteinuria and slow down renal progression. Evidence that pulse steroid plus intravenous or oral cyclophosphamide can retard the rate of progression of advanced IgAN was provided by several groups worldwide. Cyclosporin is generally not used to treat IgAN. The efficacy of azathioprine is equivocal. Mycophenolate mofetil reduces proteinuria by up to 30% and favorably impacts renal survival in Chinese patients with mild histologic lesions, but these results were not achieved in Caucasians with more advanced disease. In conclusion, the choice of immunomodulatory therapy remains controversial. We advocate the use of immunomodulatory agents as an adjunctive therapy in patients with proteinuria>1 g/day despite achieving target blood pressure with full renin-angiotensin blockade. More aggressive therapy should be reserved for patients with nephrotic-range proteinuria, crescentic lesions and/or rapidly progressive renal failure.

Effect of zinc supplementation on mycospecific immunoglobulins in tuberculosis patients.

The effect of zinc supplementation on the serum level of IgA, IgG, IgM mycospecific immunoglobulins in tuberculosis patients alongwith normal control and disease control subjects were studied. It was observed that with antituberculous drugs for one month (without zinc supplementation), the serum level of immunoglobulins in tuberculosis subjects although decreased significantly, but with zinc supplementation along with antituberculous drugs for one month the decrease in the level of immunoglobulins in serum was more significant. This may be attributed to the effect of zinc supplementation favouring the normal compartmentalisation state of iron and also to the immunomodulatory effect of zinc.

HEMA enhances IgG1 production by human B-cells in vitro.

UNLABELLED: We have previously shown that the resin monomer 2-hydroxyethylmethacrylate (HEMA) affects mouse B-lymphocyte activity, leading to increased IgG1 antibody production in vivo. In the present study, we tested, in vitro, the hypothesis that HEMA also affects human B-lymphocyte activity. The in vitro production of IgG1, IgM, and IgA in supernatants from purified human CD19+ B-lymphocyte cultures, containing different concentrations of HEMA, was assayed with ELISA. Proliferation was measured by [methyl-(3)H] thymidine incorporation. Of the different HEMA concentrations used, the lower concentrations caused a significant increase in IgG1 production, but not in IgM or IgA production, in vitro. The lower HEMA concentrations did not significantly change B-cell proliferation. At the highest concentration, HEMA significantly suppressed IgG1 and IgM production, as well as B-cell proliferation, in vitro. In conclusion, HEMA can, at certain concentrations, selectively enhance human B-lymphocyte IgG1 production. ABBREVIATIONS: 2-hydroxyethylmethacrylate (HEMA), Dulbecco's Modified Eagle's Medium supplemented with heat-inactivated fetal bovine serum, gentamycin, penicillin, and streptomycin (D-MEM++++), Enzyme-linked Immuno-sorbent Assay (ELISA), phosphate-buffered saline (PBS), ovalbumin (OVA), pokeweed mitogen (PWM), counts per minute (CPM).