Antibody Attack Research Articles

Agonist antibody to MuSK protects mice from MuSK myasthenia gravis

Myasthenia gravis (MG) is a chronic and severe disease of the skeletal neuromuscular junction (NMJ) in which the effects of neurotransmitters are attenuated, leading to muscle weakness. In the most common forms of autoimmune MG, antibodies attack components of the postsynaptic membrane, including the acetylcholine receptor (AChR) or muscle-specific kinase (MuSK). MuSK, a master regulator of NMJ development, associates with the low-density lipoprotein-related receptor 4 (Lrp4) to form the signaling receptor for neuronal Agrin, a nerve-derived synaptic organizer. Pathogenic antibodies to MuSK interfere with binding between MuSK and Lrp4, inhibiting the differentiation and maintenance of the NMJ. MuSK MG can be debilitating and refractory to treatments that are effective for AChR MG. We show here that recombinant antibodies, derived from MuSK MG patients, cause severe neuromuscular disease in mice. The disease can be prevented by a MuSK agonist antibody, presented either prophylactically or after disease onset. These findings suggest a therapeutic alternative to generalized immunosuppression for treating MuSK MG by selectively and directly targeting the disease mechanism.

#1622 Minimal changes disease and myasthenia gravis: a logical association

Abstract Background and Aims Minimal changes disease (MCD) is responsible for 10-25% of nephrotic syndrome cases in adults. It can have a primary or secondary aetiology, being associated with diseases like infections, atopy or even haematological malignancies. There is a described association between MCD and myasthenia gravis (MG) in the literature, which we will explore in this case report. Clinical Case An autonomous 67 years old female, healthy except for overweight develops diplopia and dysphagia, being diagnosed with anti-musk MG (antibodies titters 2,2002 nmol/L). Thymoma presence was excluded by CT scan. She starts oral treatment with pyridostigmine without response. Two months later she develops generalized oedema. Analytically she had normal kidney function (Cr 0.7 mg/dL; BUN 28.5 mg/dL), hypoalbuminemia (2.09 g/dL), dyslipidaemia and nephrotic proteinuria of PCR 8g/g creat, without leucoeritrocyturia. Reno-vesical echography was normal. No alterations in immunological study except for a low IgG 396 mg/dL. Anti-PLA2R was negative. Kidney biopsy was performed, having 4 glomerulus that looked normal in optical microscopy. In our centre we do not have electronic microscopy available, so the biopsy was interpreted as MCD. She started prednisolone (PDN) 1 mg/kg/day with clinical improvement and resolution of the symptoms and proteinuria (0.062 g/g creat). In November 2022, while she was tapering the PDN, she had a myasthenic crisis, with MCD recurrency. She did 5 plasmapheresis sessions, the PDN dose was increased to 1 mg/kg/day and two rituximab administrations (1000 mg each) were done. There was an improvement in MG symptoms during 3 weeks and then she aggravated again. The proteinuria slowly decreased during 6 weeks until RPC 1.3 g/g creat and then started to aggravate when the corticosteroids were tapered. It was decided to initiate mycophenolate mofetil (MMF), there was improvement and both diseases are controlled until today, the patient is asymptomatic under 7.5 mg/day of prednisolone, with a PCR 0.2 g/g creat. Discussion The production of a circulating permeability factor by abnormal T cells, that causes the podocytes damage, is one of the possible explanations for MCD. There are reports of improvements with plasmapheresis (PF) by permeability factor remotion from circulation. MG is also caused by T cells antibodies attack, but the attack occurs against channels essential for the neuromuscular membrane function. The similarities of the mechanisms make the existence of a common branch in the t cells dysregulation seem plausible. Anti musk MG is very responsive to PF but it has a limited effect in time. Rituximab depletes B cells responsible for promoting the impaired T cells responses. It has been associated with longer remissions in cortico-sensitive MCD with relapsing disease. The exact same mechanism occurs when rituximab is used in MG. In this case the patient did not have a satisfactory response to rituximab as the patient kept dependent of high PDN doses, so we decided to initiate MMF with a complete remission of both pathologies and allowing the use of lower PDN doses. Take Home Message The association between MCD and myasthenia gravis is rare, especially in patients without thymoma. When we analyse the diseases physiopathology, we find common mechanisms that can justify the association. The identification of this relation can be advantageous making possible early rituximab use, that has been showing good results in both pathologies. In this particular clinical case, there was a recurrence with rituximab when we tapered the PDN, so the patient started MMF with good response and allowing lower PDN doses.

Immune mediated myasthenia gravis in children, current concepts and new treatments: A narrative review article.

Myasthenia gravis (MG) is the most frequent transmission disease in the neuromuscular junction. Juvenile myasthenia gravis (JMG) is an autoimmune antibody-mediated disease of postsynaptic endplate defined as MG presentation in patients before the age of 18 years old. While many clinical features of JMG are identical to the adults, there are some significant differences between them regarding presentation, clinical course, antibody level, and thymus histopathology. In JMG, ocular symptoms are more frequent, the clinical course is comparably benign, and the outcome is better than adult MG. Antibodies attack the muscle endplate proteins in the postsynaptic membrane and interfere with transmission. These antibodies in most patients are against the acetylcholine receptors, but they may also be directed toward muscle-specific kinase, lipoprotein-related protein 4, and agrin. Findings show racial influences and genetic effects on the occurrence of JMG. The essential clinical symptom is fatigable weakness of muscles that can be in the form of isolated ocular type or more disseminated weakness. The diagnosis of JMG is essentially clinical, with fluctuating patterns of weakness and easy fatigability, but a series of diagnostic evaluations can confirm the diagnosis. Precise diagnostic evaluation and distinction from congenital myasthenic syndromes is critical. The treatment plan is conducted according to the clinical course (ocular or generalized), antibody type, and disease severity. The mainstay of treatment includes symptomatic therapy, long-lasting immunosuppressive treatment and treatment of myasthenic crisis. Novel medications are introduced and conducted to the specific pathophysiologic mechanisms of the disease, and they are used primarily in the refractory MG.

Modeling the contribution of antibody attack rates to single and dual helminth infections in a natural system

Within-host models of infection can provide important insights into the processes that affect parasite spread and persistence in host populations. However, modeling can be limited by the availability of empirical data, a problem commonly encountered in natural systems. Here, we used six years of immune-infection observations of two gastrointestinal helminths (Trichostrongylus retortaeformis and Graphidium strigosum) from a population of European rabbits (Oryctolagus cuniculus) to develop an age-dependent, mathematical model that explicitly included species-specific and cross-reacting antibody (IgA and IgG) responses to each helminth in hosts with single or dual infections. Different models of single infection were formally compared to test alternative mechanisms of parasite regulation. The two models that best described single infections of each helminth species were then coupled through antibody cross-immunity to examine how the presence of one species could alter the host immune response to, and the within-host dynamics of, the other species. For both single infections, model selection suggested that either IgA or IgG responses could equally explain the observed parasite intensities by host age. However, the antibody attack rate and affinity level changed between the two helminths, it was stronger against T. retortaeformis than against G. strigosum and caused contrasting age-intensity profiles. When the two helminths coinfect the same host, we found variation of the species-specific antibody response to both species together with an asymmetric cross-immune response driven by IgG. Lower attack rate and affinity of antibodies in dual than single infections contributed to the significant increase of both helminth intensities. By combining mathematical modeling with immuno-infection data, our work provides a tractable model framework for disentangling some of the complexities generated by host-parasite and parasite–parasite interactions in natural systems.

Dynamic HIV-1 spike motion creates vulnerability for its membrane-bound tripod to antibody attack

Vaccines targeting HIV-1’s gp160 spike protein are stymied by high viral mutation rates and structural chicanery. gp160’s membrane-proximal external region (MPER) is the target of naturally arising broadly neutralizing antibodies (bnAbs), yet MPER-based vaccines fail to generate bnAbs. Here, nanodisc-embedded spike protein was investigated by cryo-electron microscopy and molecular-dynamics simulations, revealing spontaneous ectodomain tilting that creates vulnerability for HIV-1. While each MPER protomer radiates centrally towards the three-fold axis contributing to a membrane-associated tripod structure that is occluded in the upright spike, tilting provides access to the opposing MPER. Structures of spike proteins with bound 4E10 bnAb Fabs reveal that the antibody binds exposed MPER, thereby altering MPER dynamics, modifying average ectodomain tilt, and imposing strain on the viral membrane and the spike’s transmembrane segments, resulting in the abrogation of membrane fusion and informing future vaccine development.

Is ABO Compatibility Important in Islet Transplantation?

One of the current criteria for clinical islet allotransplantation is ABO blood group compatibility between donor and recipient.1 The distribution of ABH antigens in human pancreata was first examined >40 y ago, revealing expression in acinar and vascular cells but not in islets.2 This underlined the importance of ABO matching in whole pancreas transplantation, but the situation in islet transplantation is more complicated. Although islets in situ appear to be ABH-negative,2 islets prepared for transplant are invariably contaminated with exocrine tissue including acinar cells. Furthermore, it is not known whether the islet isolation and transplantation process itself influence ABH expression. It is therefore somewhat surprising that ABH expression in islet preparations before and after transplant has not been characterized until now. In this issue of Transplantation, Verhoeff et al3 present a detailed immunohistochemical and flow cytometric survey of ABH antigen levels in human pancreatic tissue, isolated human clinical-grade islets, and islets derived from human embryonic stem cells (hESCs). After confirming that ABH antigens are present on acinar cells but not on endocrine and ductal cells in the pancreas, the authors demonstrate that islet preparations consist primarily of ABH-negative endocrine cells but are significantly contaminated with ABH-positive acinar cells. When islets were transplanted into immunodeficient rats, the endocrine component was ABH-negative at 24 wk, whereas remnant acinar tissue stained positive. Pancreatic endocrine progenitors derived from hESCs were ABH-negative and remained so after in vivo maturation following transplantation into rats, although this was not unexpected given that the hESC donor was blood group O. The human-to-immunodeficient rat islet xenograft model used in the latter part of the study does have some limitations. First, the kidney subcapsular site does not accurately reflect the clinical scenario, in which islets are transplanted intraportally.1 Subcapsular delivery co-localizes the islets with acinar tissue fragments and potentially exposes the islets to “bystander” injury and inflammation when anti-ABH antibodies attack the acinar cells. In contrast, intraportal delivery disperses islets and acinar fragments widely throughout the liver microvasculature, which probably minimizes co-localization and thus reduces the likelihood of bystander effects. Furthermore, subcapsular but not intraportal delivery shields the graft from exposure to anti-ABH IgM antibodies. Although these differences are not relevant in the immunodeficient rat model, they may well be relevant in the clinical setting. Second, the immunodeficient rat model does not allow investigation of the importance of the in vivo anti-ABH immune response to islet grafts. I have worked with one of the authors (L.J.W.) to develop a mouse model of anti-A antibody-mediated rejection of transgenic blood group A-expressing cardiac grafts.4 However, these A-transgenic donor mice are unsuitable for examining anti-A–mediated islet graft rejection because expression of the antigen is endothelial cell-restricted and absent on islets. Humanized mouse models may be more appropriate, as suggested by the authors. The take-home message of this interesting paper is that ABO matching is indeed likely to be important in islet allotransplantation—as is the case for HLA matching5—but may become less so if islet purification efficiency improves sufficiently or if hESC-derived islets are used. On the former point, the authors speculate that the restriction of surface expression of ABH antigens to acinar tissue (starkly illustrated by Figure 6A in the paper) provides an opportunity to enrich the purity of A, B, or AB islets by some form of negative selection. Although practicality at scale may be an issue, this is an intriguing proposition that is worthy of further consideration.

Evan’s Syndrome: Case Series with Review of Literature

Evans syndrome is a rare autoimmune disease in which an individual’s antibodies attack the body’s own red blood cells and platelets. It is characterised by simultaneous or sequential development of Immune Thrombocytopenic Purpura (ITP) and Autoimmune Hemolytic Anemia (AIHA) with positive Direct Antiglobulin test (DAT). AIHA can be cold, warm or mixed type depending on the type of antibody. 80% of total AIHA cases are warm AIHA. Warm AIHA is mostly caused by IgG antibody which reacts at 370 C. Warm AIHA is associated with classical case of Evan’s syndrome. Some variants of Evan’s syndrome are associated with leucocytosis. The current article discusses 3 cases of Evan’s syndrome, all presenting differently - Classical Evan’s syndrome, Evan’s syndrome associated with leucocytosis and Evan’s syndrome associated with neuropathic pain. In this case series, pathophysiology, workup done at blood centre and blood component transfusion support in patients with Evan’s syndrome has been discussed. Keywords: Evan’s syndrome, Anemia, Autoimmune

Antiphospholipid Antibodies and Lipids in Hematological Malignancies.

One of the main groups of lipids is phospholipids, which are mainly involved in forming cell membranes. Neoplastic processes such as cell replication have increased lipid synthesis, making tumor cells dependent on this synthesis to maintain their requirements. Antiphospholipid antibodies attack phospholipids in the cell membranes. Three main types of antiphospholipid antibodies are recognized: anti-β2 glycoprotein I (anti-β2GP-I), anticardiolipin (aCL), and lupus anticoagulant (LA). These types of antibodies have been proven to be present in hematological neoplasms, particularly in LH and NHL. This review on antiphospholipid antibodies in hematological neoplasms describes their clinical relationship as future implications at the prognostic level for survival and even treatment.

Understanding and management of anti-N-methyl-D-aspartate receptor encephalitis from a child psychiatry perspective: report of five cases

ABSTRACT Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is a rare autoimmune entity in psychiatry literature that occurs when antibodies attack NMDA-type glutamate receptors in the brain. Principle clinical features include a neurological domain such as seizure, orofacial dyskinesia, dystonia, and choreic-like movements of extremities. Also the psychiatric manifestations of this form of encephalitis may vary from psychotic-like symptoms to mood symptoms like depression or mania. Herein we report on five female child cases diagnosed with anti-NMDAR encephalitis, presented with both neurological and psychiatric clinical picture, and highlight the trajectory of disorder from a psychiatric perspective.

Epilepsy in patients with MOG antibody disease

Introduction. MOG (anti-myelin oligodendrocyte glycoprotein) antibody disease is a group of demyelinating disorders of the central nervous system, in which antibodies attack the glycoproteins on the oligodendrocyte myelin membrane. The aim of the study was to evaluate the course of the disease in patients with MOG antibody disease with epilepsy.
 Materials and methods. We examined 11 patients (5 men and 6 women) with MOG antibody disease aged from 2 months to 46 years. Three case studies were described when patients with MOG antibody disease had epileptic seizures.
 Results and discussion. Epileptic seizures preceded the diagnosis of MOG antibody disease in the first patient. The disease presented as right-sided optic neuritis in the second patient. Seven years later, an epileptic seizure occurred after childbirth, when the BBB could have become permeable to circulating MOG antibodies. The disease presented with headache in the third patient. Right-sided optic neuritis and ataxia developed after an acute viral respiratory infection. Myelitis was diagnosed, and an epileptic seizure occurred one year later. The patient had a combination of CADASIL syndrome with MOG antibody disease.
 Conclusion. Epileptic seizures are common in patients with MOG antibody disease. In addition to antiepileptic therapy, treatment of MOG antibody disease is crucial. This leads to good seizure control and a favourable prognosis.

EPIDEMIOLOGY OF AUTOIMMUNE THYROID DISEASE

Most diseases involve many genes in complex interactions, in addition to physical and cultural environmental factors. If a disease is caused by genetic and environmental factors, its etiological origin can be referred to as having a multifactorial pattern. The common multifactorial diseases encompass environmental inuences on the causal processes. Thyroid is a multifactorial type of origin of disease. The epidemiological studies show that if thyroid disease is caused by the interaction of both genetic and environmental factors, then mostly it is autoimmune thyroid disease. When the antibodies attack the thyroid gland, it is called Auto Immune Thyroid Disease (AITD). The present study attempts to examine whether the occurrence of thyroid disease in a micro area is due to autoimmune conditions. To prove the fact clinically, blood of thyroid patients were collected and tested in a laboratory. The result shows that most of the patients have autoimmune thyroid disease. Moreover, some environmental and genetic factors were also examined since thyroid disease is a multifactorial origin of disease.

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

Psychiatric manifestations of anti-N-methyl-D-aspartate receptor encephalitis: A case report.

A Case Report: Rare Presentation of Intracranial Hemorrhage post Guillain Barré Syndrome

Background: Guillain Barre Syndrome (GBS) is an autoimmune disease where antibodies attack the myelin sheath of peripheral nerves. The hallmark of the disease includes symmetrical quadriparesis, respiratory distress, and failure with subsequent need for mechanical ventilation. Most cases occur after a viral or bacterial infection. Other causes, such as intracranial hemorrhage, also exist, and several case studies report an association between these two pathologies. Case Report: In this report, we present the case of an elderly male patient with intracranial (IC) bleeding post-GBS. The patient was admitted to the hospital for dyspnea and diagnosed with pneumonia. When he started complaining of progressive bilateral ascending paralysis of his lower extremities, we performed a lumbar puncture, and he was diagnosed with GBS. We started him on intravenous immune globulins (IVIGs) immediately, but his weakness progressed to include his respiratory muscles, and he required mechanical ventilatory support with Intensive Care Unit (ICU) admission. We extubated him after two weeks, but he needed to be reintubated 24 hours later for a severely decreased level of consciousness. An urgent computed tomography scan of the brain showed IC bleeding. The patient developed a septic shock due to his pneumonia, which was refractory to antibiotics and vasopressors. He passed away a few weeks after that. Conclusion: Our case represents a unique type of association between IC hemorrhages and GBS, where the bleeding occurred several days after, as opposed to before GBS. It also reinforces the correlation between GBS and Intracranial bleeding and stresses the importance of having a high index of suspicion when facing either pathology since both have similar symptoms that may overlap or mask each other.

An Antibody Attack against Body Wasting in Cancer

Cachexia is a devastating, non-curable condition in many cancer patients that is marked by severe wasting of the muscle and fat tissue. Its prevention has been hampered by an insufficient knowledge of the underlying molecular mechanism(s) that lead to its pathogenesis. Suriben etal. (2020) now report the development and characterization of an antagonistic antibody for the previously identified GDF15-GFRAL axis that efficiently blocks tumor-induced body wasting in experimental animals.

Central Diabetes Insipidus in a Patient with Stiff Person Syndrome

Background: Central diabetes insipidus (CDI) is a rare hypothalamic-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis of which more than one third of etiologies are unidentified. Autoimmunity is associated with one third of patients with apparently idiopathic CDI. The most common antibody detected in auto immune CDI is autoantibodies to AVP-secreting cells (AVPcAb). Stiff-person syndrome (SPS) is a rare neurological disorder with features of an autoimmune disease. It is characterized by fluctuating muscle rigidity in the trunk and limbs and a heightened sensitivity to stimuli. It is well known that SPS is associated with multiple auto immune endocrinopathy including auto immune diabetes and auto immune thyroid disease. The association between SPS and CDI is not well documented in the literature. Case information: We report a case of 51 year old female who developed CDI while being treated for SPS unmasked by high dose steroids. Result: Anti amphiphysin is the only antibody detected in our patient. Animal studies showed a high expression of amphiphysin in anterior and posterior pituitary gland, data in human are still vague .One theory is that anti-amphiphysin antibodies attack the amphiphysin molecules in the AVP secreting cells and inhibit release of AVP. Conclusion: This antibody could hint towards the autoimmune cause of CDI.

Zika virus-induced neuro-ocular pathology in immunocompetent mice correlates with anti-ganglioside autoantibodies

ABSTRACT A severe consequence of adult Zika virus (ZIKV) infection is Guillain-Barré Syndrome (GBS), where autoreactive antibodies attack peripheral and central nervous systems (CNS) resulting in neuro-ocular pathology and fatal complications. During virally induced GBS, autoimmune brain demyelination and macular degeneration correlate with low virus neutralization and elevated antibody-mediated infection among Fcγ-R bearing cells. The use of interferon-deficient mice for ZIKV studies limits elucidation of antibody-dependent enhancement (ADE) and long-term pathology (≥120 days), due to high lethality post-infection. Here we used immunocompetent BALB/c mice, which generate robust humoral immune responses, to investigate long-term impacts of ZIKV infection. A high infectious dose (1x106 FFU per mouse) of ZIKV was administered intravenously. Control animals received a single dose of anti-IFNAR blocking monoclonal antibody and succumbed to lethal neurological pathology within 13 days. Immunocompetent mice exhibited motor impairment such as arthralgia, as well as ocular inflammation resulting in retinal vascular damage, and corneal edema. This pathology persisted 100 days after infection with evidence of chronic inflammation in immune-privileged tissues, demyelination in the hippocampus and motor cortex regions of the brain, and retinal/corneal hyperplasia. Anti-inflammatory transcriptional responses were tissue-specific, likely contributing to differential pathology in these organs. Pathology in immunocompetent animals coincided with weakly neutralizing antibodies and increased ADE among ZIKV strains (PRVABC59, FLR, and MR766) and all Dengue virus (DENV) serotypes. These antibodies were autoreactive to GBS-associated gangliosides. This study highlights the importance of longevity studies in ZIKV infection and confirms the role of anti-ganglioside antibodies in ZIKV-induced neuro-ocular disease.

Thrombocytopenic purpura on an organic farm with pen mating: a case report on the re-emergence of an old disease

BackgroundThrombocytopenia is an immune-mediated disease, which affects suckling piglets. Piglets are pale and inactive, show multiple hemorrhages and often die within days. Pathological examination reveals severe haemorrhages and oedema in several organs. Severe thrombocytopenia and elongated bleeding time characterize the disease haematologically.The sow produces antibodies against the thrombocyte antigens of the boar, which are present in the blood of the piglets. These isoimmune antibodies attack the platelets and megakaryocytes of the piglets, causing thrombocytopenia in succeeding matings of the same boar and sow. There is no known therapy against this condition. In the last few decades, the disease has become rare due to the increase of artificial insemination.Case presentationOn an organic breeding farm in Switzerland with a high percentage of natural pen matings, piglets of three litters showed haemorrhages on the skin, prolonged bleeding time and were generally in a reduced general state. A pathological examination revealed multifocal haemorrhages in the stomach, kidneys, dermis, mesenterium and spinal cord. Haematology showed a massive thrombocytopenia and regenerative anaemia. Due to these findings the diagnosis of thrombocytopenic purpura was established.To avoid further matings of the same boar and sow and thus more affected piglets, out of three possible boars the responsible sire had to be determined. This was achieved through array genotyping and subsequent computation of identity by descent and calculation of Mendelian errors for parentage verification. Thereby the responsible boar was identified and as a consequence removed from the farm. Further preventive measures, that had been established, included the recording of all matings and regular exchange of boars.ConclusionThe decreased number of natural matings with the surge of artificial insemination has probably reduced the number of cases of thrombocytopenic purpura and thus the disease awareness of farmers and veterinarians. However, as consumers wish for better animal welfare and higher ecological standards we may see a rise in natural matings and thus a return of the disease. In case of affected litters, genetic testing was proven a valid method for investigation and prevention of more cases and may be used more in the future.

Paraneoplastic ataxic syndrome with anti-Yo antibodies in breast and ovarian cancer: A retrospective analysis.

e18089 Background: Paraneoplastic cerebellar syndrome is a rare immunological reaction caused most commonly by Anti-Yo or Purkinje cell cytoplasmic antibody type 1(PCA1) to cerebellar degeneration protein 2(CDR2), found in the cerebellum and ectopically produced by tumor. Most cases are reported in women with HER2+ breast and ovarian cancers with underlying breast cancer patients having relatively better prognosis. Treatment initiation within one month of symptom onset has shown better outcomes. Methods: A retrospective analysis was conducted using a clinical database at a single institution and included 3 patients with a cancer diagnosis and ataxic symptoms diagnosed between 2016 and 2020. Data collection included age, gender, performance status, site of disease, pathology, diagnostic work up, treatment and overall survival (OS). Results: The study included 3 patients who presented with new onset ataxic symptoms with the median time of cancer diagnosis from onset of symptoms being 5 months (range 4-7). Median age was 62 years (range 59-83), all 3 patients were females and functionally independent before symptom onset. Out of 3 patients 2 had HER2+ breast cancer (one with IHC 3+ and one with equivocal IHC but 20 HER2 signals/nucleus) and the third had ovarian carcinoma. All 3 patients had stage IIIA disease as per AJCC 8th edition and presented with bilateral extremity weakness, ataxia, visual disturbances, vertigo and nausea/vomiting. Extensive neurological work up including MRI brain, CSF analysis, EEG were inconclusive except for high titres of anti- Yo antibodies in all patients. All patients were treated with cancer directed therapy and immunomodulation with plasma exchange, IVIG and steroids. The median OS being 22 months (range 12-28) with 2 patients with underlying breast cancer alive at the time of the analysis albeit there has been no neurological recovery, despite IVIG, steroids, and plasma exchange. Conclusions: The anti-Yo associated paraneoplastic ataxic syndrome most commonly associated with breast and pelvic tumors in women has a very poor prognosis despite anti-tumor and immunomodulating therapies, leaving most patients bed-ridden. The neurologic damage is irreparably incurred once the antibodies attack cerebellar cells. Thus, it is critical for clinicians to recognize the potential signs and symptoms as early as possible, so that treatment can be started, and long term symptoms are minimized. Further studies are needed to know the exact mechanism of this syndrome and provide evidence based treatment options.

Good Pasture Syndrome-A Case Presentation

Good pasture syndrome (GPS), also known as Pneumorenal Syndrome or anti-glomerular basement membrane disease, is a rare autoimmune disease in which antibodies attack the basement membrane in lungs and kidneys, leading to bleeding from the lungs and kidney failure. Currently, the preferred term for both conditions is “anti-GBM antibody disease”. Circulating antibodies are directed against the collagen of the part of the kidney known as the glomerular basement membrane (GBM), leading to bleeding from the lungs and kidney failure. Antibodies also attack the collagen of the air sacs of the lung (alveoli) resulting in bleeding of the lung (pulmonary hemorrhage). Good pasture syndrome is fatal unless quickly diagnosed and treated. (Magalini SI, et al, 1997)

Central Diabetes Insipidus in a Patient with Stiff Person Syndrome

Background: Central diabetes insipidus (CDI) is a rare hypothalamic-pituitary disease due to the deficiency of arginine vasopressin (AVP) synthesis of which more than one third of etiologies are unidentified. Autoimmunity is associated with one third of patients with apparently idiopathic CDI. The most common antibody detected in auto immune CDI is autoantibodies to AVP-secreting cells (AVPcAb). Stiff-person syndrome (SPS) is a rare neurological disorder with features of an autoimmune disease. It is characterized by fluctuating muscle rigidity in the trunk and limbs and a heightened sensitivity to stimuli. It is well known that SPS is associated with multiple auto immune endocrinopathy including auto immune diabetes and auto immune thyroid disease. The association between SPS and CDI is not well documented in the literature. Case information: We report a case of 51 year old female who developed CDI while being treated for SPS unmasked by high dose steroids. Result: Anti amphiphysin is the only antibody detected in our patient. Animal studies showed a high expression of amphiphysin in anterior and posterior pituitary gland, data in human are still vague .One theory is that anti-amphiphysin antibodies attack the amphiphysin molecules in the AVP secreting cells and inhibit release of AVP. Conclusion: This antibody could hint towards the autoimmune cause of CDI.