Immunoglobulin Infusion Research Articles

Implikacje diagnostyczne oraz skuteczne leczenie w przebiegu zespołu Susac’a z trombofilią

Susac syndrome is an uncommon autoimmune microangiopathy characterized by a combination of encephalopathy, branch retinal artery occlusions (BRAO), and hearing loss. In this report, we present a detailed history of a 31-year-old man with Susac syndrome with thrombophilia. The diagnosis was based on clinical signs and neurological, otolaryngological and ocular examination. Fluorescence retinal angiography showed right BRAO. A slight (30 dB) sensorineural lowering of the hearing level was observed in the audiogram. Numerous ovoid lesions in the corpus callosum were detected in magnetic resonance (MR). The applied treatment included glucocorticosteroids, disease-modifying antirheumatic drugs, anticoagulant treatment and immunoglobulin infusions. After treatment, ophthalmologic symptoms receded, the recanalization of BRAO was detected in angiography, and the lesions in the corpus callosum were reduced in control MR. To date, this is the first report showing the effective treatment of Susac syndrome, which was confirmed simultaneously in MR and fluorescein angiography in a case of Susac syndrome with thrombophilia.

Efficacité et bonne tolérance du rituximab sur un purpura thrombopénique immunologique chronique révélant un syndrome de délétion 22q11

Introduction22q11 deletion is a common genetic disorder which associates a polymalformative syndrome to dysimmune features. Autoimmunity and immune deficiency manifestations are often associated, resulting in a therapeutic challenge for this disease. Case reportWe report a 28-year-old patient who presented with hemorrhagic manifestations leading to the diagnosis of severe thrombocytopenia (15,000/mm3), of both central and peripheral origin. Patient history, cardio-facial malformative syndrome, hypoparathyroidism and partial immune deficiency led to the molecular diagnosis of 22q11 deletion syndrome. After failure of polyvalent immunoglobulin infusions, rituximab alone allowed the increase of platelets to their usual level of 100–120,000/mm3 within 4 weeks and a complete clinical remission of the hemorrhagic syndrome, without any infectious complication after a 4-year follow-up. ConclusionRituximab may be an alternative to corticosteroid for the treatment of auto-immune manifestations associated with minor forms of 22q11 deletion syndrome without significant worsening of the immune deficiency.

Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IgG) (IGHy) in Patients with Primary Immunodeficiency Disease (PIDD): Infections over Time

Efficacy of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IgG) (IGHy) in Patients with Primary Immunodeficiency Disease (PIDD): Infections over Time

Local Adverse Reaction Rates Decreased over Time during Treatment with Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IGHy) in Patients with Primary Immunodeficiency Disorders in the IGHy Phase 3 Studies

Local Adverse Reaction Rates Decreased over Time during Treatment with Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IGHy) in Patients with Primary Immunodeficiency Disorders in the IGHy Phase 3 Studies

Real-World Use of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IG) (IGHy) in Patients with Primary Immunodeficiency Disorders (PIDD)

Real-World Use of Recombinant Human Hyaluronidase-Facilitated Subcutaneous Infusion of Immunoglobulin G (IG) (IGHy) in Patients with Primary Immunodeficiency Disorders (PIDD)

Ijar Successful Treatment of Neuropathic Pain and Mood Symptoms with Duloxetine in a Patient with West Nile Virus Infection

Neuropathic pain and concomitant mood disorder in West Nile Virus (WNV) infection seem difficult to control. A 57years old female diagnosed with neuroinvasive WNV infection presented with burning pain in the hands and feet consistent with neuropathic pain. In addition, a Patient Health Questionnaire-2 (PHQ-2) depression screening questionnaire administered to her was positive and on further interview she met diagnostic criteria for a mood disorder due to a general medical condition. Her symptoms included a loss of pleasure in all activities and mood lability. During her course of treatment, she also underwent five months of intensive physical therapy for rehabilitation and received intravenous immunoglobulin infusions for flaccid paralysis secondary to an inflammatory peripheral neuropathy attributed to WNV infection. The neuropathic pain and mood disorder dramatically disappeared after using duloxetine. Duloxetine is recommended for neuropathic pain management especially in patients with WNV infection.

Intravenous immunoglobulin therapy in a selective IgG3 deficient patient with recurrent respiratory infections and asthma attacks

The IgG subclass deficiency is defined as a significant decrease in the serum concentrations of one or more subclasses of IgG in a patient whose total IgG concentration is normal. IgG subclass deficiency can predispose to recurrent sinopulmonary infections. A 29-year-old female patient with a 4-year history of bronchial asthma presented with cough, sputum, dyspnea, and recurrent respiratory infections. She had frequently been treated with antibiotics and systemic steroids for recurrent respiratory infections and acute asthma exacerbations. Chest X-ray and computed tomography showed pectus excavatum and bronchial wall thickening without lung parenchymal abnormalities. On immunological evaluation, she was found to have a low serum IgG3, with normal total IgG concentration. Under diagnosis of selective IgG3 deficiency, she was started on monthly infusions of intravenous immunoglobulin (IVIG) therapy. The frequency and severity of respiratory infections and acute asthma exacerbations were markedly decreased during 3 years of IVIG therapy. Our case report suggests that a patient who has underlying selective IgG3 deficiency and asthma may benefit from IVIG therapy as this can significantly reduce the incidence and severity of recurrent respiratory infections and acute asthma exacerbations. (Allergy Asthma Respir Dis 2016;4:225-229)

Subcutaneous Immunoglobulin Therapy in a Woman with Spontaneous Pregnancy Loss and Multiple Sclerosis

Background: Off-label use of intravenous immunoglobulin has been reported for the treatment of recurrent spontaneous pregnancy loss and selected cases of multiple sclerosis. However, the use of subcutaneous immunoglobulin has not been reported in these settings. Methods and results: We report on tolerability and clinical efficacy of subcutaneous immunoglobulin therapy in a woman with the unusual association of IgG4 subclass deficiency, C4 hypocomplementemia, localized scleroderma, unexplained spontaneous pregnancy loss and multiple sclerosis. Weekly infusions of subcutaneous immunoglobulin were self-administered at home (6 grams/week, Hizentra®) during the next pregnancy after abortion. Interferon beta-1a for the treatment of relapsing-remitting multiple sclerosis was stopped before pregnancy. During pregnancy only subcutaneous immunoglobulin was administered. The patient was found to have 4% of CD3+CD16/CD56+ (Natural Killer (NK) /T cells). The patient delivered a healthy baby (Apgar score 9 at 5 minutes) at 37 weeks gestation. During pregnancy and 3 months follow-up after delivery no multiple sclerosis flare-ups were observed. NK-T cell percentages remained stable. Conclusions: Our observation indicates that subcutaneous immunoglobulin therapy was well tolerated and efficacious in a selected case of unexplained abortion and multiple sclerosis.

A 2-month-old boy with hemolytic anemia and reticulocytopenia following intravenous immunoglobulin therapy for Kawasaki disease: a case report and literature review

Herein, we report a rare case of hemolytic anemia with reticulocytopenia following intravenous immunoglobulin therapy in a young infant treated for Kawasaki disease. A 2-month-old boy presented with fever lasting 3 days, conjunctival injection, strawberry tongue, erythematous edema of the hands, and macular rash, symptoms and signs suggestive of incomplete Kawasaki disease. His fever resolved 8 days after treatment with aspirin and high dose infusion of intravenous immunoglobulin. The hemoglobin and hematocrit decreased from 9.7 g/dL and 27.1% to 7.4 g/dL and 21.3%, respectively. The patient had normocytic hypochromic anemia with anisocytosis, poikilocytosis, immature neutrophils, and nucleated red blood cells. The direct antiglobulin test result was positive, and the reticulocyte count was 1.39%. The patient had an uneventful recovery. However, reticulocytopenia persisted 1 month after discharge.

Haemolytic Anaemia Following High Dose Intravenous Immunoglobulin Treatment for Epidermolysis Bullosa Acquisita

Background: Epidermolysis bullosa aquisita (EBA) is a severe acquired blistering skin disease that is often resistant to prednisolone but can respond well to intravenous immunoglobulin infusion (IVIg). Main Observations: We describe the case of a 35 years old male patient with EBA who developed clinically significant haemolytic anaemia with a drop in Hb from 15.3 g/dL to a nadir of 8.4 g/dL within 5 days post IVIg infusion. The patient was blood group A and the IVIg batch was found to have a high titre of anti-A immunoglobulin. Conclusions: IVIg is an effective treatment for EBA. Haemolysis associated with IVIg has not previously been reported in the dermatology literature but review of data from other specialties shows that the problem is well recognised. Dermatologists using IVIg should be aware of this potential complication and patients should be consented appropriately and warned about this potential side effect.

Colon Adenoma Implicating Myasthenia Gravis: A Case Report of a Patient with Postcolectomy Complications.

We report the case of a 63-year-old patient with myasthenia gravis (MG) due to acetylcholine receptor antibodies (AChR) who underwent colectomy due to colon adenoma and developed myasthenic crisis and anastomosis leakage after surgery. The patient underwent two plasma exchanges, 4 and 6 days preoperatively, and received intravenous prednisolone and immunoglobulin infusion due to the crisis, which included primarily bulbar symptoms. The patient developed on the 10th postoperative day bowel obstruction symptoms and anastomosis leakage which required surgical repair and ileostomy. Bowel obstruction occurred in a patient with AChR related myasthenia after plasma exchange and during immunosuppression although it is more commonly reported in patients with thymoma related myasthenia.

The history and evolution of immunoglobulin products and their clinical indications

The history of providing antibodies to treat diseases began in the 19th century with the discovery of tetanus and diphtheria toxins and the demonstration that immunity to tetanus and diphtheria infections could be transferred by immune sera. Characterization of the mediators of this immunity resulted in the discovery that antibodies are proteins that can be isolated and used to protect against infectious diseases. Development of a method to isolate antibodies from human plasma that could be safely injected into people initiated the development of human gamma globulin preparations to provide antibodies to patients with inherited antibody deficiencies. To overcome the limitations imposed by intramuscular injection of gamma globulin, intravenous gamma globulin preparations were developed that began to be used in a wide variety of clinical conditions. Thus the original clinical indication for infection prevention was expanded to several other indications that employ large doses to suppress inflammatory and autoimmune disorders. The most recent development in immunoglobulin therapy is the production of concentrated immune globulins for subcutaneous injection. Home infusions of subcutaneous immunoglobulin are increasingly used to treat immunodeficient patients and are being studied for other clinical applications.

Anti-TNF alpha medications and neuropathy.

We studied the clinical, electrophysiological, and pathological features, outcome, and frequency of anti-tumor necrosis factor alpha (a-TNF) medications-induced neuropathies (ATIN) in patients with inflammatory disorders. Of 2,017 patients treated with a-TNF medication, 12 patients met our inclusion criteria for a prevalence of 0.60% and an incidence of 0.4 cases per 1,000 person-years. The median time from a-TNF medication treatment to ATIN was 16.8 months (range 2-60 months). Six patients had focal or multifocal peripheral neuropathies. The other six had generalized neuropathies. For all, a-TNF medication was stopped. Seven patients received immunoglobulin infusions. ATIN outcome was favorable in all but one patient. ATINs are rare and heterogeneous neuropathies. In 10 patients, the neuropathy was "inflammatory", suggesting that it could be due to systemic pro-inflammatory effects of a-TNF agents.

NK cell compartment in the peripheral blood and spleen in adult patients with primary immune thrombocytopenia

Immune thrombocytopenic purpura (ITP) is a disease characterized by antibody-mediated platelet destruction. The T- and B-cell subsets have been extensively studied in primary ITP, but the NK cell compartment has been less thoroughly explored. We investigated the NK cell receptor repertoire and the functionality of NK cells in the peripheral blood and spleen in patients with primary ITP. An immunophenotypic analysis of peripheral blood lymphocytes from patients revealed that the numbers of CD19+ B lymphocytes, CD4+ and CD8+ T lymphocytes and CD3−CD56+ NK cells were within the normal range. No major alteration to the expression of distinct inhibitory or activating NK cell receptors was observed. The functionality of NK cells, as evaluated by their ability to degranulate in conditions of natural cytotoxicity or antibody-dependent cell cytotoxicity (ADCC), was preserved in these patients. By contrast, these stimuli induced lower levels of IFNγ production by the NK cells of ITP patients than by those of healthy controls. We then compared the splenic NK cell functions of ITP patients with those of cadaveric heart-beating donors (CHBD) as controls. The splenic NK cells of ITP patients tended to be less efficient in natural cytotoxicity conditions and more efficient in ADCC conditions than control splenic NK cells. Finally, we found that infusions of intravenous immunoglobulin led to the inhibition of NK cell activation through the modulation of the interface between target cells and NK cells.

Referral Center for Primary Immune Deficiencies in Adults: Its Stepwise Development at the Department of Immunology- Histocompatibility, Evagelismos General Hospital

The Department of Immunology-Histocompatibility of “Evagelismos” Hospital since its beginning in 1978 showed an interest for the study of patients with primary immunodeficiencies. The cases referred and diagnosed in the Department were mainly adult patients with primary antibody deficiencies. As the number of these cases increased, the development of a Referral Center was begun. In 1999 The Central Health Council of Greece approved the establishment of a “Specialized Center for adult cases with primary immunodeficiencies” as part of the Department of Immunology-Histocompatibility. However, it was only in 2007 that the Center was officially recognized by the Ministry of Health. The services provided by the Center included among others complete laboratory investigation for the diagnosis and classification of primary immunodeficiency, an outpatient clinic, collaboration with other departments of the hospital for the replacement therapy of patients with intravenous infusions of immunoglobulin and their hospitalization for various complications of their disease. During 42 years of follow up, 208 cases with primary antibody deficiency were diagnosed which included 92 cases with common variable immunodeficiency, 78 with selective IgA-deficiency, 24 with IgG subclass deficiency, and 14 with IgA and IgG subclass deficiency. The building of a Registry of these patients according to the procedures outlined by the European Society for Immunodeficiencies had been started but it has not yet been completed. For its optimal function, this Center should be supported by the State in order to have the necessary specialized staff for the management of patients and a better organization for their hospitalization according to their needs.

Post-exposure passive immunisation for preventing rubella and congenital rubella syndrome.

To assess the effectiveness of intramuscular injection or intravenous infusion of polyclonal immunoglobulins of human sera or plasma origin for preventing rubella and congenital rubella syndrome when administered to exposed susceptible people before the onset of disease.

Rasmussen's encephalitis: A case report

A 2-year-old boy presented with left sided partial motor seizures with progressive hemiparesis. Over time, he lost speech. Magnetic resonance imaging revealed progressive atrophy of the right brain hemisphere. Monthly immunoglobulin infusion in addition to antiepileptic drugs resulted in some improvement of his weakness and speech.

Subacute encephalitis in a child seropositive for alpha-3 subunit of neuronal nicotinic acetylcholine receptors antibody

A previously healthy and developmentally normal 5-year-old boy from Saudi Arabia presented with a 3 mo history of abnormal behavior in the form of hyperactivity, decreased social engagement, episodic aggressiveness, decreased cognitive performance in school, inappropriate laughter and talking to himself, insomnia, tics and other stereotyped behaviors. His clinical neurological examination did not reveal any focal neurological deficits, but a prolonged electroencephalogram showed non-specific slowing over the right hemisphere. A diagnosis of encephalopathy was entertained, and he underwent testing for infectious, toxic, metabolic and mitochondrial disorders. Magnetic resonance imaging of the brain and cerebrospinal fluid studies were all normal. However, a comprehensive evaluation of paraneoplastic antibodies from cerebrospinal fluid demonstrated the presence of antibodies against the alpha-3 subunit of the neuronal nicotinic acetylcholine receptor, a finding also documented by tests from two different laboratories. An extensive diagnostic investigation that included a fludeoxyglucose-positron emission tomography scan for malignancies showed negative results. The patient was treated with plasmapheresis treatments (five ex- changes) that resulted in a significant improvement in his clinical picture. Following his initial treatments, the patient continued to receive monthly infusions of intravenous immunoglobulin. An evaluation at 5.5 mo after initiation of first treatment revealed a considerable improvement of his behavior and language abilities. The patient returned to his school where he has performed satisfactorily. To our knowledge, this is the first report of a child who developed sub-acute cognitive and neurobehavioral re- gression in association with the presence of a serum antibody to a neuronal ganglionic nicotinic acetylcholine receptor and who improved after immunotherapy.

Cardiac rhythm abnormalities during intravenous immunoglobulin G(IVIG) infusion in two newborn infants: coincidence or association?

Key Clinical MessageWe report the occurrence of supraventricular tachycardia during intravenous immunoglobulin (IVIG) infusion. Supraventricular tachycardia was observed in two newborn patients during IVIG infusion. Both of the babies responded to adenosine treatment. Cardiorespiratory monitoring during IVIG infusion can be recommended because of the possibility of this potentially lifethreatening adverse effect.

Use of romiplostim in patients with chronic idiopathic thrombocytopenic purpura during perioperative period.

In patients with chronic idiopathic thrombocytopenic purpura (cITP), the platelet count tends to be quite variable and, in the majority of cases, specific therapy is not warranted on a regular basis. However, patients with low platelet count (<30 nL) or with bleeding complications would require therapy, such as prednisolone, intravenous immunoglobulin infusions, splenectomy and/or immunosuppression. Romiplostim, a thrombopoietin agonist, has also proven to be useful in improving platelet counts. cITP can be associated with bleeding complications perioperatively. As such, a higher platelet count is warranted (approximately 80 nL), particularly for invasive surgeries, such as orthopaedic surgery, cardio-thoracic surgery, head and neck surgery and abdominal surgery, where risk of bleeding is quite high already. The aim of this study is to evaluate the safety and efficacy of short-term use of romiplostim, perioperatively. Patients with chronic ITP requiring major surgical interventions were enrolled in the study. Patients with malignancies or myelodysplastic syndromes, major bleeding disorders, under 18 years of age or pregnancy were excluded. This study has shown that the use of romiplostim is safe and effective in improving platelet counts preoperatively and that this could achieve excellent haemostasis, with no associated bleeding complications or rebound thrombocytopenia. A larger study involving multiple centres is required to verify these findings.