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1.
Activating Antibodies to The Calcium-sensing Receptor in Immunotherapy-induced Hypoparathyroidism.
Lupi, I, Brancatella, A, Cetani, F, Latrofa, F, Kemp, EH, Marcocci, C
The Journal of clinical endocrinology and metabolism. 2020;(5)
Abstract
CONTEXT Immune checkpoint inhibitors (ICIs), such as programmed cell death protein-1 (PD-1), programmed cell death protein-ligand 1 (PD-L1), and cytotoxic T lymphocyte antigen-4 (CTLA-4) monoclonal antibodies, are approved for the treatment of some types of advanced cancer. Their main treatment-related side-effects are immune-related adverse events (irAEs), especially thyroid dysfunction and hypophysitis. Hypoparathyroidism, on the contrary, is an extremely rare irAE. OBJECTIVES The aim of the study was to investigate the etiology of autoimmune hypoparathyroidism in a lung cancer patient treated with pembrolizumab, an anti-PD-1. METHODS Calcium-sensing receptor (CaSR) autoantibodies, their functional activity, immunoglobulin (Ig) subclasses and epitopes involved in the pathogenesis of autoimmune hypoparathyroidism were tested. RESULTS The patient developed hypocalcemia after 15 cycles of pembrolizumab. Calcium levels normalized with oral calcium carbonate and calcitriol and no remission of hypocalcemia was demonstrated during a 9-month follow-up. The patient was found to be positive for CaSR-stimulating antibodies, of IgG1 and IgG3 subclasses, that were able to recognize functional epitopes on the receptor, thus causing hypocalcemia. CONCLUSION The finding confirms that ICI therapy can trigger, among other endocrinopathies, hypoparathyroidism, which can be caused by pathogenic autoantibodies.
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2.
[Three cases report of juvenile dermatomyositis with positive anti-melanoma differentiation associated gene 5 (MDA5) antibody and severe interstitial lung disease and literature review].
Hou, J, Zhou, ZX, Li, JG, Xu, YJ, Ding, YC
Zhonghua er ke za zhi = Chinese journal of pediatrics. 2019;(12):928-933
Abstract
Objective: To report the clinical features of anti-MDA5 antibody positive juvenile dermatomyositis (JDM) complicated with severe interstitial lung disease (ILD). Methods: The clinical data of three patients, who was admitted to the Department of Rheumatology and Immunology, Children's Hospital of the Capital Institute of Pediatrics from September 2016 to July 2017, with anti-melanoma differentiation associated gene 5 (MDA5) antibody positive JDM complicated with ILD were retrospectively extracted and analyzed. Meanwhile, PubMed database, CNKI, Wanfang database and China Biology Medicine disc (from their establishment to February 2019) with the key words "juvenile dermatomyositis" "interstitial lung disease" , and "anti-MAD5 antibody" both in English and Chinese were searched. Results: There were 2 females and 1 male (P1-P3), aged from 10 years 3 months to13 years 4 months, the time from onset to diagnosis were 2 months, 4 months and 10 months. All presented with rash. One of them had decreased muscle strength, and two had decreased activity tolerance. Creatine kinase was 588, 915 and 74 U/L, and serum ferritin were 1 792, >2 000 and 195.4 μg/L. All three patients had positive anti-MDA5 antibodies. At the time of diagnosis, all of them had ILD, pneumothorax and mediastinal emphysema, but had no respiratory symptoms. All three patients received oral methylprednisolone and cyclophosphamide pulse therapy, while human immunoglobulin was given only to P1 and P2. P1 developed rapid progressive pulmonary interstitial disease (RPILD) and died of respiratory failure after 2 months. While P2 and P3 were followed up for 1 to 2 years, who had complete remission, as anti-MDA5 antibody turned to negative and ILD improved significantly. Ten related reports in literature were retrieved, without reported Chinese cases, and most cases initiated with rash and very likely complicated with arthritis. Some of them were more likely to have ILD rather than muscle weakness. It also showed that Japanese JDM children had higher rate of positive anti-MDA5 antibody than patients from the U.S. and U.K., and are more susceptible to ILD and RPILD. The mortality rate of patients with RPILD is extremely high. Conclusions: The cases of JDM with positive anti-MDA5 antibody mainly presented with rash and mild muscle weakness, and could be complicated with ILD, pneumothorax and mediastinal emphysema without respiratory symptoms at early stage. Anti-MDA5 antibody titer is related to disease activity and can turn to negative after treatment.
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Autoimmune hypoglycemia due to anti-insulin antibodies.
Veiguela Blanco, B, Felechosa, MD, García Moreira, V
Medicina clinica. 2018;(12):e43-e44
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Insulin autoimmune syndrome (Hirata's disease) in an Italian patient: a case report and review of the literature.
Censi, S, Albergoni, MP, Gallo, N, Plebani, M, Boscaro, M, Betterle, C
Clinical chemistry and laboratory medicine. 2018;(6):889-895
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Abstract
We describe the case of a 54-year-old Caucasian Italian male experiencing episodes of hypoglycemia, occurring mainly after meals. He had never been exposed to insulin and was taking ramipril, flecainide and acetylsalicylic acid. An oral glucose tolerance test (OGTT) showed high blood glucose levels diagnostic for diabetes mellitus at 120 min and hypoglycemia with inappropriately high insulin levels at 240 min. The 72-h fasting test, abdominal computed tomography (CT) and positron emission tomography-CT were normal. Insulin autoantibodies were positive at high titers, prompting a diagnosis of insulin autoimmune syndrome (IAS). The patient was advised to take frequent, small meals and thus achieved a good control of his hypoglycemic symptoms. After 18 months of this dietary management, his insulin autoantibody levels decreased considerably but remained detectable. During an OGTT, his blood glucose levels at 120 min were now indicative of an impaired glucose tolerance rather than diabetes, and there was improvement in the glucose nadir. The patient had no other clinical or latent autoimmune diseases. Here we discuss the main features of IAS (also known as Hirata's disease) and review the cases of IAS reported in Italy to date.
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Case report on pathogenetic link between gluten and IgA nephropathy.
Costa, S, Currò, G, Pellegrino, S, Lucanto, MC, Tuccari, G, Ieni, A, Visalli, G, Magazzù, G, Santoro, D
BMC gastroenterology. 2018;(1):64
Abstract
BACKGROUND A relationship between IgA nephropathy (IgAN) and celiac disease (CD) has been reported. We show the pathogenetic link for the first time. CASE PRESENTATION A 39-year-old man with cystic fibrosis (CF) and CF-related diabetes started to present gross hematuria, back pain and headache. At admission, laboratory analysis showed increase in serum creatinine of 1.5 mg/dl, together with hematuria and mild proteinuria (1 g/24 h). He underwent a renal biopsy to investigate the cause of hematuria and renal failure. Biopsy was consistent with IgAN. In view of patient reported dyspepsia, an upper gastrointestinal endoscopy with duodenal biopsies was undertaken and was normal. We looked for mucosal deposits of tTG-2 in the duodenum and the renal mesangium. tTG-2 deposits were found both in the duodenum and in renal biopsies, where they topographically replicated mesangial IgA deposits. After one year on a continued gluten containing diet, the patient developed a Marsh 2 type duodenal pathology. CONCLUSIONS Our findings suggest a connection between CD and IgAN in terms of an immune-mediated gluten-induced pathogenesis even in the absence of villous atrophy and serum celiac autoantibodies.
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Expanding spectrum of contactin-associated protein 2 (CASPR2) autoimmunity-syndrome of parkinsonism and ataxia.
Kannoth, S, Nambiar, V, Gopinath, S, Anandakuttan, A, Mathai, A, Rajan, PK
Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology. 2018;(3):455-460
Abstract
Contactin-associated protein 2 (CASPR2) antibodies are originally associated with Morvan's syndrome and peripheral nerve hyper excitability. Our objective was to study retrospectively the clinical spectrum of CASPR2 antibody-positive patients in our hospital. This is a retrospective observational study. Patients treated at the Amrita Institute of Medical Sciences from May 2013 to April 2016, who were tested positive for CASPR2 antibodies, were included. A total of 1584 samples were tested in the neuroimmunology laboratory during the study period for voltage-gated potassium channel (VGKC) complex antibodies-leucine-rich glioma-inactivated protein 1 (LGI1) and CASPR2 antibodies. Thirty-four were positive for LGI1, 13 were positive for CASPR2, and 7 were for both (total 54-3.4% positivity). Of these 54 cases, 11 were treated in our hospital. Seven were positive for LGI1, three for CASPR2, and one for both. The patient who had both CASPR2 and LGI1 antibody positive had Morvan's syndrome. One patient with CASPR2 had neuromyotonia. The other patient was admitted with status epilepticus with a syndrome of parkinsonism and ataxia. The third patient had encephalopathy and myoclonus with a syndrome of parkinsonism and ataxia. Two of them underwent siddha treatment for other ailments prior to the onset of the disease for other ailments. Our short series shows the expanding spectrum of CASPR2 autoimmunity. Syndrome of parkinsonism and ataxia is an important manifestation of CASPR2 autoimmunity where we can offer a definitive treatment.
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Medical Nutrition Therapy Is Effective in the Management of Hypoglycemia Caused by Insulin Antibodies: A Case Report and Literature Review.
Li, R, Mao, J, Yu, K, Wang, L, Hu, M, Xu, L
Journal of the American College of Nutrition. 2016;(1):86-90
Abstract
Autoimmune antibodies, induced by exogenous insulin preparations, may result in labile glucose control and frequent hypoglycemia in some rare cases. In addition to insulin cessation, immune suppressants and/or plasmapheresis have been used as the primary remedies for these patients. Some previous studies also indicate that the condition tends to remit spontaneously after discontinuation of insulin exposure. Because of this, the clinical importance of nutritional interventions and behavioral approaches, which may play a role in ameliorating the symptoms, should also be emphasized. Herein, we report on a 64-year-old man with hypoglycemia induced by insulin antibodies (IAs), whose hypoglycemic symptoms significantly improved after the implementation of nutrition therapy. This rare case expands our knowledge of the management of hypoglycemia, and for the first time highlights the significance of nutritional and lifestyle intervention in treatment of IA-induced hypoglycemia.
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Screening for MOG-IgG and 27 other anti-glial and anti-neuronal autoantibodies in 'pattern II multiple sclerosis' and brain biopsy findings in a MOG-IgG-positive case.
Jarius, S, Metz, I, König, FB, Ruprecht, K, Reindl, M, Paul, F, Brück, W, Wildemann, B
Multiple sclerosis (Houndmills, Basingstoke, England). 2016;(12):1541-1549
Abstract
BACKGROUND Histopathological studies have revealed four different immunopathological patterns of lesion pathology in early multiple sclerosis (MS). Pattern II MS is characterised by immunoglobulin and complement deposition in addition to T-cell and macrophage infiltration and is more likely to respond to plasma exchange therapy, suggesting a contribution of autoantibodies. OBJECTIVE To assess the frequency of anti-myelin oligodendrocyte glycoprotein (MOG), anti-M1-aquaporin-4 (AQP4), anti-M23-AQP4, anti-N-methyl-d-aspartate-type glutamate receptors (NMDAR) and 25 other anti-neural antibodies in pattern II MS. METHODS Thirty-nine serum samples from patients with MS who had undergone brain biopsy (n = 24; including 13 from patients with pattern II MS) and from histopathologically non-classified MS patients (n = 15) were tested for anti-MOG, anti-M1-AQP4, anti-M23-AQP4, anti-NMDAR, anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-type glutamate receptors (AMPAR), anti-gamma-aminobutyric acid receptors (GABABR), anti-leucine-rich, glioma-activated protein 1 (LGI1), anti-contactin-associated protein 2 (CASPR2), anti-dipeptidyl-peptidase-like protein-6 (DPPX), anti-Tr/Delta/notch-like epidermal growth factor-related receptor (DNER), anti-Hu, anti-Yo, anti-Ri, anti-Ma1/Ma2, anti-CV2/collapsin response mediator protein 5 (CRMP5), anti-glutamic acid decarboxylase (GAD), anti-amphiphysin, anti-Ca/RhoGTPase-activating protein 26 (ARHGAP26), anti-Sj/inositol-1,4,5-trisphosphate receptor 1 (ITPR1), anti-Homer3, anti-carbonic anhydrase-related protein (CARPVIII), anti-protein kinase gamma (PKCgamma), anti-glutamate receptor delta 2 (GluRdelta2), anti-metabotropic glutamate receptor 1 (mGluR1) and anti-mGluR5, as well as for anti-glial nuclei antibodies (AGNA) and Purkinje cell antibody 2 (PCA2). RESULTS Antibodies to MOG belonging to the complement-activating immunoglobulin G1 (IgG1) subclass were detected in a patient with pattern II MS. Detailed brain biopsy findings are shown. CONCLUSION This is the largest study on established anti-neural antibodies performed in MS so far. MOG-IgG may play a role in a small percentage of patients diagnosed with pattern II MS.
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Autoantibody-mediated encephalitis: Not just paraneoplastic, not just limbic, and not untreatable.
Jammoul, A, Li, Y, Rae-Grant, A
Cleveland Clinic journal of medicine. 2016;(1):43-53
Abstract
Autoantibody-mediated encephalitis is a heterogeneous group of recently identified disorders, all caused by autoimmunity directed against components of the central nervous system. Despite severe and even prolonged neurologic deficits, dramatic improvements may occur with aggressive treatment.
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A case of late-onset, thymoma-associated myasthenia gravis with ryanodine receptor and titin antibodies and concomitant granulomatous myositis.
Stefanou, MI, Komorowski, L, Kade, S, Bornemann, A, Ziemann, U, Synofzik, M
BMC neurology. 2016;(1):172
Abstract
BACKGROUND Myasthenia gravis is an autoimmune neuromuscular disorder, which has only rarely been reported to co-manifest with myositis. The diagnosis of concomitant myositis in patients with myasthenia gravis is clinically challenging, and requires targeted investigations for the differential diagnosis, including EMG, autoantibody assays, muscle biopsy and, importantly, imaging of the mediastinum for thymoma screening. CASE PRESENTATION This report presents a case-vignette of a 72-year-old woman with progressive proximal muscle weakness and myalgias, diagnosed with thymoma-associated myasthenia and bioptically verified granulomatous myositis, with positive autoantibody status for ryanodine receptor and titin antibodies. CONCLUSIONS The diagnosis of concurrent myositis and myasthenia gravis, especially in the presence of ryanodine receptor and titin antibodies, should lead neurologists to adopt different treatment strategies compared to those applied in myasthenia or myositis alone. Moreover, further evidence is warranted that titin and, particularly, ryanodine receptor antibodies may co-occur or be pathophysiologically involved in myasthenia-myositis cases.