Production Of Autoimmune Antibodies Research Articles

Safety of Antithyroid Drugs in Avoiding Hyperglycemia or Hypoglycemia in Patients With Graves' Disease and Type 2 Diabetes Mellitus: A Literature Review.

Graves' disease (GD) may increase the difficulty of glucose control in patients with type 2 diabetes mellitus (T2DM). Therefore, selecting a drug with limited blood glucose side effects is an important issue in patients with T2DM and GD. Antithyroid drugs (ATDs)including propylthiouracil (PTU), methimazole, and carbimazoleare commonly prescribed for the treatment of GD. Here, we review and summarize the literature from the last 10 years and discuss the effects of current ATDs used for GD for blood glucose control in patients with T2DM. A search of the literature published between January 1, 2012 and December 1, 2022 was conducted using three major medical databases: Google Scholar, Ovid Medline, and Scopus. An initial search was conducted on PubMed using the MeSH terms "propylthiouracil," "methimazole," "carbimazole," and "hyperglycemia" or "hypoglycemia" in academic databases. All articles included "Graves' disease" and "type 2 diabetes mellitus" in the title. Based on the results of previous studies, the hyperglycemic andhypoglycemic side effects of ATDs can be explained by several possible mechanisms. The most widely accepted hypothesis is that sulfhydryl group drugs (e.g., methimazole and carbimazole) cleave the disulfide bond of insulin and enhance its immunogenicity, resulting in hypoglycemia. Moreover, some reports have indicated that methimazole is associated with hypoglycemia; therefore, if the patient has a history of autoimmune diseases, it is necessary to consider whether to change drugs or actively track the production of autoimmune antibodies. Innon-diabetic and diabetic patients with GD, the hyperglycemic and hypoglycemic side effects of PTU (on glycemic variation) were less than that of thiamazole. However, as relatively few reports have investigated the side effects of blood sugar changes, further research is necessary to confirm these effects. In addition to autoimmune diseases, drug side effects may need to be considered. These findings provide considerations for clinicians to select more appropriate ATDs for patients with GD and T2DM, and implement improved care guidelines.

Leocarpinolide B Attenuates Collagen Type II-Induced Arthritis by Inhibiting DNA Binding Activity of NF-κB.

Rheumatoid arthritis (RA) is a chronic autoimmune disease triggered by a cascading inflammatory response. Sigesbeckia Herba (SH) has long been utilized as a traditional remedy to alleviate symptoms associated with rheumatism. Our previous study found that leocarpinolide B (LB), a sesquiterpene lactone isolated from the whole plant of SH, possesses potent a anti-inflammatory effect on macrophages. This study was designed to evaluate the therapeutic effects of LB on RA, and further investigate the underlying mechanisms. In collagen type II-induced arthritic mice, LB was demonstrated to decrease the production of autoimmune antibodies in serum and inflammatory cytokines in the joint muscles and recover the decreased regulatory T lymphocytes in spleen. Moreover, LB significantly suppressed the inflammatory infiltration, formation of pannus and bone erosion in the paw joints. In vitro testing showed that LB inhibited the proliferation, migration, invasion, and secretion of inflammatory cytokines in IL-1β-induced human synovial SW982 cells. Network pharmacology and molecular docking suggested NF-κB p65 could be the potential target of LB on RA treatment, subsequent experimental investigation confirmed that LB directly interacted with NF-κB p65 and reduced the DNA binding activity of NF-κB in synovial cells. In conclusion, LB significantly attenuated the collagen type II-induced arthritis, which was at least involved in the inhibition of DNA binding activity of NF-κB through a direct binding to NF-κB p65. These findings suggest that LB could be a valuable lead compound for developing anti-RA drugs.

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Effects of COVID-19 and vaccination on the human immune system: cases of lymphopenia and autoimmunity

Telitacicept following plasma exchange in the treatment of subjects with recurrent neuromyelitis optica spectrum disorders: A single‐center, single‐arm, open‐label study

IntroductionNeuromyelitis optica spectrum disorders (NMOSD), mainly mediated by B cells and AQP4 antibody, has a high rate of recurrence. Telitacicept is a novel drug specifically targeting the upstream signaling for the activation of B cell with its following production of autoimmune antibodies. Thus, it may be a promising approach. Our study preliminarily explored the potential safety and effectiveness of Telitacicept following plasma exchange in the treatment of recurrent NMOSD.MethodsThis was a single‐center, single‐arm, open‐label study enrolling eight patients with recurrent NMOSD in China. All patients received plasma exchange three times, followed by Telitacicept 240 mg every week for 46 times. The primary endpoint was the time of first recurrence after enrollment. Secondary end points included: changes in Expanded Disability Status Scale score, Optic Spinal Impairment Scale score, Hauser Ambulation Index, number of lesions on MRI, retinal nerve fiber layer thickness measured by optical coherence tomography, latency and amplitude of visual evoked potential, titer of AQP4 antibody, and immune parameters of blood. Safety was also assessed. The study was registered with Chictr.org.cn (ChiCTR1800019427).ResultsEight eligible patients were enrolled. Relapse occurred in two patients (25%) and five patients (63%) remained relapse free after 48 weeks of treatment. The time to first recurrence was prolonged and the number of recurrences was reduced (p < 0.001, power of test = 1). One patient withdrew from the study due to low neutrophil count. No serious adverse events occurred.ConclusionsIn this small, uncontrolled study, Telitacicept following plasma exchange has the potential to be a safe treatment for patients with recurrent NMOSD. It may prolong the recurrence interval and reduces the annual count of recurrences. A multicenter randomized controlled study with a larger sample is thus feasible and needed to further assess its safety and efficacy.

Myasthenia Gravis: A Rare Neurologic Complication of Immune Checkpoint Inhibitor Therapy.

Myasthenia gravis is an autoimmune disorder affecting the neuromuscular junction, which is characterized by the production of autoimmune antibodies to acetylcholine or muscle-specific kinase receptors, causing an error in transmission of nerve impulses to various muscles. The hallmark of myasthenia gravis is “grave or serious” fluctuating muscle weakness. Ocular, respiratory, bulbar, and skeletal muscles are most commonly affected; therefore, patients often present with fatigable ptosis, blurry vision, diplopia, change in facial expression, dysphagia, dysarthria, dyspnea, and limb weakness. Many medications, including fluroquinolone, aminoglycoside, magnesium sulfate, quinidine, and select beta blockers, are known to unmask or exacerbate symptoms of myasthenia gravis. Although the pathogenesis is not entirely understood, T lymphocytes are thought to play a role by blocking the acetylcholine receptors and causing antibody production. In the era of new immune-modulating therapies emerging for treatment of different cancers, their role in inducing a proinflammatory state has become apparent, thus highlighting a clear need to increase awareness about their role in inducing myasthenia gravis or myasthenia-like symptoms.

Obesity Accelerates Age Defects in Human B Cells and Induces Autoimmunity.

Aging is associated with systemic inflammation and decreased production of protective antibodies while the production of autoimmune antibodies is increased. Our results have shown that the human obese adipose tissue (AT), which increases in size with aging, contributes to systemic and B cell intrinsic inflammation, reduced protective and increased pathogenic B cell responses leading to increased secretion of autoimmune antibodies.With this R56 funding, we have been able to investigate the cellular and molecular mechanisms by which the human obese AT induces intrinsic B cell inflammation and dysfunctional B cell responses, stimulates the secretion of autoimmune antibodies, whose specificity has been characterized, and engages different AT cell types in antigen presentation pathways to allow secretion of these autoimmune antibodies. Briefly, immune cells are recruited to the AT by chemokines released by both non-immune (adipocytes) and by resident and infiltrating immune cells. We have identified several mechanisms responsible for the release of “self” antigens, and we have shown that reduced oxygen availability and hypoxia, cell cytotoxicity and DNA damage induce cell death and lead to further release of pro-inflammatory cytokines, “self” protein antigens, cell-free DNA and lipids. We have also identified different antigen presenting cells in the AT, responsible for the activation of pathogenic B cells, class switch and secretion of autoimmune IgG antibodies. The experiments performed have allowed the discovery of novel mechanisms for pathogenic responses and the identification of pathways to target in order to promote better humoral immunity during aging.

Hyper\u2010metabolic B cells in the spleens of old mice make antibodies with autoimmune specificities

BackgroundAging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known.MethodsSplenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer.ResultsResults have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion.ConclusionsThese results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.

Metabolic requirements of human pro-inflammatory B cells in aging and obesity.

The subset of pro-inflammatory B cells, called late memory, tissue-like or double negative (DN), accumulates in the blood of elderly individuals. Here we show that DN B cells do not proliferate and do not make antibodies to influenza antigens, but they secrete antibodies with autoimmune reactivity, in agreement with their membrane phenotype (CD95+CD21-CD11c+) and their spontaneous expression of the transcription factor T-bet. These cells also increase in the blood of individuals with obesity and autoimmune diseases, but causative mechanisms and signaling pathways involved are known only in part. In the present paper we compare frequencies and metabolic requirements of these cells in the blood of healthy individuals of different ages and in the blood and the subcutaneous adipose tissue (SAT) of individuals with obesity. Results show that DN B cells from young individuals have minimal metabolic requirements, DN B cells from elderly and obese individuals utilize higher amounts of glucose to perform autoimmune antibody production and enroll in aerobic glycolysis to support their function. DN B cells from the SAT have the highest metabolic requirements as they activate oxidative phosphorylation, aerobic glycolysis and fatty acid oxidation. DN B cells from the SAT also show the highest levels of ROS and the highest levels of phosphorylated AMPK (5’-AMP activated kinase) and Sestrin 1, both able to mitigate stress and cell death. This metabolic advantage drives DN B cell survival and function (secretion of autoimmune antibodies).

Mechanisms for secretion of antibodies with “anti-self” reactivity by the human obese adipose tissue

Abstract We have shown that the human obese subcutaneous adipose tissue(SAT)contributes to systemic and B cell intrinsic inflammation and increased secretion of autoimmune antibodies. Immune cells are recruited to the SAT by chemokines released by both adipocytes and infiltrating immune cells. We have identified several mechanisms responsible for the release of “self” antigens in the human obese SAT, induction of class switch and production of autoimmune antibodies, such as hypoxia, NK cell cytotoxicity and DNA damage, which induce cell death and further release of pro-inflammatory cytokines. All these processes, in the context of an inflammatory environment like the obese SAT, stimulate the production of autoimmune IgG antibodies which have been described to be pathogenic. We have identified “self” antigens that stimulate the secretion of autoimmune antibodies in cultures of SAT-derived immune cells, using a Protein G immunoprecipitation protocol to purify the autoantibodies, combined with mass spectrometry. Results show that around 25% of these “self” antigens are found at high frequency in all the individuals evaluated so far in independent experiments. Moreover, &amp;gt;90% of these “self” antigens (lipid and protein antigens, DNA, RNA) are cytoplasmic, nuclear or membrane-associated. These results allow the identification of novel pathways to manipulate in order to decrease pathogenic immune responses during aging.

The Role of Follicular Helper T Cell Molecules and Environmental Influences in Autoantibody Production and Progression to Inflammatory Arthritis in Mice.

Antibody-mediated autoimmunity involves cognate interactions between self-reactive T cells and B cells during germinal center (GC) reactions. The aim of this study was to determine the role of essential follicular helper T (Tfh) cell molecules (CXCR5, signaling lymphocytic activation molecule-associated protein) on autoreactive CD4+ cells and the role of certain environmental influences that may determine GC-driven autoantibody production and arthritis development. We transferred self-reactive CD4+ cells from KRN-Tg mice into recipient mice, which induced autoantibodies and autoinflammatory arthritis. This model allowed manipulation of environmental effects, such as inflammation, and use of transferred cells that were genetically deficient in important Tfh cell-associated molecules. A deficiency of signaling lymphocytic activation molecule-associated protein (SAP) in CD4+ cells from KRN-Tg mice completely protected against arthritis, indicating that stable T cell-B cell interactions are required for GC formation, autoantibody production, and arthritis induction. In contrast, a CXCR5 deficiency in CD4+ cells from KRN-Tg mice still induced disease when these cells were transferred into wild-type mice, suggesting that T cell help for B cells could rely on other migration mechanisms. However, various manipulations influenced this system, including elimination of bystander effects through use of CD28(-/-) recipient mice (reduced disease) or use of inflammation-inducing Freund's complete adjuvant (progression to arthritis). We also examined the capacity of preexisting GCs with a nonautoimmune specificity to co-opt autoimmune T cells and observed no evidence for any influence. In addition to the quality and quantity of cognate CD4+ cell help, external factors such as inflammation and noncognate CD4+ cell bystander activation trigger autoimmunity by shaping events within autoimmune GC responses. SAP is an essential molecule for autoimmune antibody production, whereas the importance of CXCR5 varies depending on the circumstances.

Asthma and hypoxia

More or less severe asthma attacks can damage the CNS and peripheral system in adults and children, both directly causing hypoxia and indirectly with the production of autoimmune antibodies. The pathogenic mechanism is still unknown; cytokines, TNFs, interleukins, free radicals and nitric oxide are often involved as causative factors for the disorders [1,2]. In this review we focus our attention on the relationship between atopy and CNS (central) or PNS (peripheral system) involvement. The main disorders associated with atopic disease are: Atopic myelitis Hopkins syndrome Hirayama disease Spinal progressive muscular atrophy (SPMA) The occurrence of myelitis in patients with atopic diathesis (atopic myelitis) affecting young adults has been widely reported especially in Japan.[2,3] In general, the disorders affect the posterior column of the cervical spinal cord, as shown clinically and by an MRI, and are characterized by hyperIgEaemia and the presence of light antigen-specific IgE. Another disease that has been reported in association with atopic disorders is Hirayama disease, a juvenile muscular atrophy of the distal upper extremity, which is also associated with airway allergies such as allergic rhinitis and atopic asthma. Our group reported on a 13-year-old girl who had recurrent acute episodes of myelitis after asthma attacks; the patient showed to be affected by Hopkins syndrome [4] (HS); a flaccid paralysis affecting one or more limbs after an asthma attack. It is a poliomyelitis-like illness, with frequent recurrences in which a possible link between the disease and atopic myelitis was reported, but until now the precise etiopathogenetic mechanism still remains unknown. Prospective study on the history of allergic disorders in known neurological diseases, an association between spinal progressive muscular atrophy and asthma as well as between myelitis and atopic dermatitis has been demonstrated. Central nervous system damage associated with atopic diathesis may be classified into two categories: eosinophilic myelitis mainly affecting the cervical spinal cord and those lower motor neuron, such as Hopkins syndrome, Hirayama disease and SPMA [2,4]. Recently we reported children with epileptic crisis related to cow's milk protein allergy; this disease can manifest itself with skin reactions, failure to thrive, and anaphylaxis as well as gastrointestinal and respiratory disorders [5]. In conclusion, the aim of this report is to analyse current data on the link between asthma and CNS/or PNS involvement and also, cow's milk protein allergy and epileptic events, highlighting the presence and scientific evidence for any potential pathogenetic mechanism.

IMO-8400, a novel TLR7, TLR8 and TLR9 antagonist, inhibits disease development in lupus-prone NZBW/F1 mice (119.12)

Abstract Several studies have implicated Toll-like receptors (TLRs) 7, 8 and 9 in the development and progression of lupus. We have developed IMO-8400, a synthetic DNA-based antagonist that has shown potent inhibition of TLR7-, TLR8-, and TLR9-mediated immune responses in cell-based assays and in non-human primates. To assess the therapeutic potency of IMO-8400, we have tested this compound in lupus-prone NZBW/F1 mice. Mice were injected subcutaneously with IMO-8400 at 1.9, 3.8 or 7.5 mg/kg once a week or 7.5 mg/kg once every two weeks from the age of week 21 to 33, and sacrificed at week 34. NZBW/F1 mice treated with IMO-8400 at the weekly dose of 3.8 or 7.5 mg/kg or 7.5 mg/kg every two weeks showed a significant reduction in urine protein and blood urea nitrogen levels in compression to that of untreated mice. Additionally, anti-DNA, anti-RNP and anti-SM IgG levels were also lower in treated mice than untreated controls. No treatment-related side-effects were observed. Histological examination of kidney sections revealed improvement in nephritis (reduced glomerular sclerosis and decreased interstitial inflammation), accompanied by decreased glomerular deposits of IgG immune complex in mice treated with IMO-8400. These results indicate that IMO-8400 suppressed autoimmune antibody production and improved renal function by inhibiting immune responses in lupus-prone NZBW/F1 mice. Thus, IMO-8400 has the potential for the treatment of lupus and other autoimmune diseases.

Circulating B lymphocytes producing autoantibodies to endothelial cells play a role in the pathogenesis of Takayasu arteritis

Takayasu arteritis (TA) is an autoimmune disease with an unclear etiology and pathophysiology. An antibody-mediated inflammatory response is a known feature of this disease, however, the role of circulating B-lymphocyte production of such antibodies is not known. The objective of this study is to characterize in vitro production of autoimmune antibodies by B-lymphocytes from patients with TA and to examine differences related to disease activity. Peripheral blood samples were taken from 72 patients with TA and 50 age-matched controls. Among the patients with TA, 42 had active disease while 31 had inactive disease. The Sharma modified criteria were used for diagnosis, and the National Institutes of Health criteria were used for TA activity assessment. Levels of autoantibodies in culture supernatant of circulating B-lymphocytes, including anti-endothelial cell antibody (AECA), anti-cardiolipin antibody (ACA), anti-beta(2) glycoprotein-I antibody (aβ₂GPI), and anti-annexin V antibody (AAVA), were assayed by enzyme-linked immunosorbent assay (ELISA) in each participant. In vitro levels of AECA, ACA, aβ₂GPI, and AAVA from circulating B-lymphocytes were significantly increased in TA patients compared with controls (AECA: 0.6 ± 0.36 vs 0.18 ± 0.09, P < .001; ACA: 0.69 ± 0.22 vs 0.54 ± 0.13, P < .001; aβ₂GPI: 0.99 ± 0.19 vs 0.83 ± 0.07, P< .001; AAVA: 0.62 ± 0.26 vs 0.41 ± 0.44, P < .001). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in active TA were higher than those in inactive TA (AECA: 0.85 ± 0.29 vs 0.28 ± 0.10, P < .001; ACA: 0.79 ± 0.21 vs 0.56 ± 0.15, P < .001; AAVA: 0.82 ± 0.16 vs 0.36 ± 0.06, P < .001). No difference was found in the in vitro level of aβ₂GPI between active TA and inactive TA (1.01 ± 0.17 vs 0.96 ± 0.22, P = .115). In vitro levels of AECA, ACA, and AAVA from circulating B-lymphocytes in inactive TA showed no statistic difference with those in controls (AECA: 0.28 ± 0.10 vs 0.18 ± 0.09, P = .096; ACA: 0.56 ± 0.15 vs 0.54 ± 0.13, P = .699; AAVA: 0.36 ± 0.06 vs 0.41 ± 0.44, P = .200). In vitro levels of aβ₂GPI in inactive TA were higher than those in controls (0.96 ± 0.22 vs 0.83 ± 0.07, P < .001). This study characterizes in vitro production of autoantibodies by circulating B-lymphocytes from patients with TA. Differences in production from those with active versus inactive disease suggest that phenotypic alterations in this cell type may play an important role in pathogenesis.

Age-dependent, polyclonal hyperactivation of T cells is reduced in TNF-negativegld/gldmice

The generalized lymphoproliferative disorder (gld) mouse strain is characterized by severe splenomegaly/lymphadenopathy, the production of autoimmune antibodies, and the appearance of CD4/CD8-negative T cells. An additional TNF deficiency of gld/gld mice attenuates the course of the disorder through a yet-unknown mechanism. In this study, we could demonstrate that the reduced splenomegaly and lymphadenopathy in B6.gld/gld.TNF-/- mice were correlated with a decreased peripheral T cell proliferation rate and a delayed polyclonal activation. A comparative analysis of naïve T cells and memory/effector T cells showed an age-dependent difference in the T cell activation pattern in the spleen of B6.gld/gld and B6.gld/gld.TNF-/- mice. T cells from B6.gld/gld.TNF-/- spleens and lymph nodes showed significantly higher levels of CCR7 and CD62 ligand on their surface compared with B6.gld/gld mice when mice of the same age were compared. Additionally, we found an increased titer of the Th1 cytokine IFN-gamma in the serum of B6.gld/gld mice, whereas the concentration of IFN-gamma was markedly reduced in the serum of B6.gld/gld.TNF-/- mice. These findings support the hypothesis that increased T cell activation and proliferation in the presence of TNF contribute to the exacerbation of the gld syndrome.

Application of SELDI-TOF mass spectrometry in clinical evaluation of thrombotic thrombocytopenic purpura

Surface Enhanced Laser Desorption/Ionization Time Of Flight (SELDI-TOF) mass spectrometry is characterized by integration of mass spectrometry with surface chemistry, which gives rise to rapid purification and subsequent determination of protein/peptide analytes. There are several surface matrices, named proteinChips, available for analyzing a particular analyte or a subset of biomolecules in biological samples. Each proteinChip has a unique surface property suitable for fractionation of a specific group of molecules. This article demonstrates the application of SELDI-TOF for the analysis of a cleaved peptide (Mr7739 daltons) from von Willebrand Factor by a metalloproteinase, ADAMTS13. Deficiency of ADAMTS13 is a known primary risk factor for the devastating hematological disorder, Thrombotic thrombocytopenic purpura (TTP). Rapid determination of ADAMTS13 activity helps clinicians tremendously in making the correct diagnosis and initiating timely therapy. Most patients with TTP are acquired cases who exhibit a production of autoimmune antibodies against ADAMTS13 protease. TTP's clinical course is critically controlled by the autoantibody's ability to inhibit ADAMTS13 function. Thus, a second SELDI-TOF based test has been devised to measure ADAMTS13 autoantibody activity for the evaluation of TTP disease activity. In conclusion, the unique features of SELDI-TOF which allow for the examination of the role of key proteases in disease processes have opened up new doors for the clinical application of mass spectrometer based techniques.

The Gut as Site of Production of Autoimmune Antibodies

The Gut as Site of Production of Autoimmune Antibodies

The gut as site of production of autoimmune antibodies.

The gut as site of production of autoimmune antibodies.

The role of nitric oxide in mercury chloride-induced vasculitis in the brown Norway rat

Nitric oxide (NO) is an important factor in tissue trauma, but its detailed role in the pathogenesis remains unknown. In autoimmune vasculitis, it is possible that NO in one of the factors underlying tissue trauma and induction of autoimmune antibodies. To study its role on an animal model using mercury chloride (HgCl2), Brown Norway rats (BN rats) were given five injections of] HgCl2, each 1 mg/kg, over 10 days. Vasculitis and production of some autoimmune antibodies developed after HgCl2 injections. Urine nitrate/nitrite, metabolic production of NO, was produced in advance of the production of other autoimmune antibodies. To elucidate the role of NO, NG-nitro-L-arginine methyl ester (L-NAME), which is a nitric oxide synthase (NOS) inhibitor, was given in addition to HgCl2, at the daily dose of 30 mg/kg. There was no difference in production of autoimmune antibodies between this group and the control group, but urine protein excretion was suppressed in the HgCl2 + L-NAME group (p < 0.001). By immunohistochemical study, inducible NOS was positive in small vessels and mesangial cells in rat kidney. We conclude that in this animal model, over-production of NO leads to the production of autoimmune antibodies and inhibition of NOS production ameliorates proteinuria. These results suggest that NO plays an important role in the induction of renal injury in the rat model of autoimmune vasculitis.

Maternal Floor Infarction in Autoimmune Disease: Two Cases

Two cases of maternal floor infarction in women with autoimmune antibody production to various antigens are presented. We speculate that maternal floor infarction could be produced by antibodies directed against the placental urokinase plasmin system.

The autoimmune basis of dilated cardiomyopathy.

Dilated cardiomyopathy is a form of heart disease characterized by ventricular dilatation and reduced systolic function. In most patients, dilated cardiomyopathy is a sporadic disease. However, 20% of dilated cardiomyopathy patients may have a familial form of the disease. The aetiologies of both the sporadic and familial forms of dilated cardiomyopathy are unknown in most cases. Dilated cardiomyopathy has a spectrum of clinical and subclinical presentations. During the last 10 years, there have been many investigations concerning the possible aetiologic role of immune factors in dilated cardiomyopathy. It is plausible that an antecedent viral infection initiates an immunological cascade which in turn leads to production of autoimmune antibodies resulting in dilated cardiomyopathy. However, in most dilated cardiomyopathy patients, an antecedent viral infection cannot be identified. Similarly, the trail of immunological research has diverged as different groups have identified distinct autoantibodies or other immune factors in heterogeneous subsets of dilated cardiomyopathy and control patients. In this manuscript, we review the studies which have contributed supportive and confounding evidence to the theoretical autoimmune basis of dilated cardiomyopathy.