Proposed Mechanisms of Action for Intravenous Immune Globulin, Term Paper Example

Abstract

Autoimmune diseases represent a number of challenges for researchers and clinicians in establishing effective treatment strategies to improve health outcomes. The evaluation of Intravenous Immune Globulin (IVIg) is necessary to determine its effectiveness in reducing inflammation and improving the immune response for patients with autoimmune diseases. Treating these conditions requires an advanced level of knowledge and understanding in order to capture the most effective treatment method to reduce symptoms and to improve system response. The routine administration of IVIg is likely to be an effective antibody approach to use immune globulin effectively and influence the overall response to autoimmune disease. Furthermore, this approach should be considered in providing advanced therapeutics to patients who suffer from autoimmune diseases which attack and destroy antibodies and reduce immunity. It is expected that this treatment method will alleviate symptoms and create a more effective immune response to inflammation and other related concerns.

Introduction

Intravenous immune globulin (IVIg) is used as a viable treatment method for autoimmune diseases, and in particular, in the replacement of existing immune globulin for this patient population¹. It is believed by experts that replacing immune globulin on a regular basis for patients who require it is an effective means of introducing antibodies that cannot be created on their own, such as those related to various bacterial strains; as a result, the replacement of immune globulin has been used on a more expanded level to reduce the risks associated with bacterial infections that cause some types of Pneumonia or other conditions. ¹

Therefore, this type of treatment method may be useful in treating conditions in patients whose antibodies for a particular disease are not present or are inactive.¹ The following discussion will address the role of IVIg in treating autoimmune diseases, exploring this functionality and other factors in producing effective treatment outcomes for this classification of conditions.

Literature Review

IVIg is an effective treatment for conditions such as dermatomyositis.² This treatment is likely to reduce the impact of T-cell activation in patients with this condition because the introduction of IVIg will reduce the need for T-cells to activate during the immune response.² Therefore, this type of treatment should be considered during inflammatory periods so that these conditions are minimized. Furthermore, IVIg plays an important role in reducing the inflammatory response in patients so that they might better cope with this condition to treat patients with autoimmune diseases more quickly.³ The complex nature of these events provide further evidence that establishing an environment whereby T-cell activation is reduced to improve response times.³

IVIg demonstrate a substantial positive influence on patients with such conditions as Guillain-Barre Syndrome and Multifocal Motor Neuropathy.⁴  The development of this treatment alternative is based upon the concept that therapeutic antibodies have been used historically for centuries to combat some of the earliest illnesses, such as diphtheria, and that immunoglobulin replacement provides additional influence in reducing the body’s response to its own immune deficiencies in effective ways.4  From a functional point of view, this treatment method is utilized to prevent antibody suppression in some autoimmune diseases to ensure that antibodies effectively respond to the appropriate antigens.5. In some cases, B-cells inhibit the production of tumor necrosis factor and suppress auto-antibody production, while T-cells are involved in the reduction of interleukin-2 (IL-2)and interferon-y, (IFN-y) each of which contribute to disease development because their presence is no longer optimal, thereby leading to increased exposure to an immune system that is not readily protected. 4 Therefore, IVIg transmission intravenously is consistently used to inhibit continuous disease formation. 4  This type of treatment method should continue to be considered when treating a variety of autoimmune disease types in various patient populations.

IVIg is a complex phenomenon that does not have a clear understanding of action in inhibiting autoimmune diseases.5  It is known that IgG is better recognized and understood as a viable method when conducted naturally; however, the mechanism behind IVIg is less recognized and difficult to comprehend in a treatment capacity. 5 Although the specific actions of this method are not clearly understood, it is the preferred method to prevent further damage associated with autoimmune diseases. 5 In exploring these concepts further, it is important to determine how autoimmune diseases develop and what actions take place, including whether or not there are genetic conditions that may predispose some patients to these illnesses.5  The practice of understanding autoimmune diseases is challenging due to the complex nature of their causes from a cell-based perspective. Therefore, it is expected that in treating these conditions, the utilization of IVIg, in spite of gaps in knowledge, are strongly preferred. 5

IVIg also serve in a regulatory role in improving immunity and in reducing inflammation in patients with autoimmune diseases.6. These broader functions demonstrate that IVIg offer a unique and comprehensive opportunity to manage autoimmune diseases more effectively. 6 These developments provide further evidence that IVIg function in a number of ways to fight autoimmune diseases in an effective manner by suppressing symptoms and ensuring that the condition does not worsen. 6 IVIg also provide an antimicrobial function for cells which are normally targeted by autoimmune disease and is likely to improve patient outcomes in this manner.7  It is also believed that IVIg provides an opportunity for leukocytes to incorporate IVIg characteristics to improve immunity through CD22c+ cells from dendrites.8  These conditions demonstrate that an adoptive transfer process will provide further support for moving leukocytes to the necessary areas to fight autoimmune-related inflammation to alleviate symptoms. 8

In a similar manner, IVIg represent a potential opportunity to treat neurological autoimmune disorders that are sometimes difficult to manage.9 This alternative supports the development of new ideas and approaches in using IVIg to improve outcomes in clinical trials associated with these neurological autoimmune disorders. 9 Therefore, it is necessary to expand clinical trial evaluations and the utilization of IVIg in treating these conditions, particularly because the immune system is often compromised in a severe manner and the condition is difficult to manage from a treatment-based perspective.9  Patients diagnosed with Guillain-Barre Syndrome face immunity challenges of their own; however, IVIg treatment may be a viable choice in improving the immune response by reducing damage caused by the production of autoantibodies for this patient population.10. This treatment method may provide the evidence that is necessary to produce viable outcomes for patients and in supporting the development of new treatment alternatives to improve symptoms and to reduce the severity of the condition altogether.10

The safety of IVIg is likely to be questioned by some clinicians and other experts to determine if this method is applicable to a variety of autoimmune conditions. Therefore, it is important to address safety issues and concerns as early as possible prior to establishing a treatment plan to ensure that this method is appropriate. Caress, Kennedy and Eickman argue that IVIg is a relatively safe treatment regimen for patients with autoimmune disease; however, there are some complications under rare circumstances that should also be considered to determine if this is the most viable treatment method.11  These side effects, although rare, may lead to serious complications and even death in some cases; therefore, it is important for clinicians to exercise extreme caution when treating these conditions to promote successful treatment outcomes for autoimmune disease patients.11

The development of IVIg treatment achieved through the development of plasma collection activities as provided by a variety of blood donors, and is accomplished by extracting Ig and subsequent IgG from blood plasma to acquire a larger sample for treatment.12 Therefore, the purity of the treatment approach must be confirmed prior to intravenous injection into the desired patient population to enable this group of patients to experience optimal effects from the treatment itself.12 Without a purified and appropriate IVIg treatment sample, then it is likely that there could be an increased risk of side effects or other factors which could contribute to negative outcomes.12 However, this treatment alternative is one of the most useful options in providing patients with a means of alleviating symptoms and improving overall symptom management for autoimmune disease.12

The ability of IVIg to perform as an effective anti-inflammatory agent for autoimmune disease is based upon antigen recognition, which serves as a catalyst in shaping the anti-inflammatory response.13  However, higher dosage levels appear to be necessary to achieve these objectives, yet a full explanation of their pathophysiology is not clearly understood. It is believed that high levels of IgG acquisition from plasma is difficult to understand, yet different models have evolved which demonstrate its effectiveness, such as altering pathways that would normally inhibit the appropriate response. 13 Nonetheless, there is a lack of in vivo understanding of IgG in a treatment capacity and how this component impacts immunity. 13   Nonetheless, administering a high dosage of this treatment to patients is an effective tool in capturing the important anti-inflammatory properties of this treatment method, using a high dose as a marker for an effective level of response.13

The use of IVIg has also been explored for the treatment of Crohn’s Disease (CD), which is a complex condition that impacts the digestive system. In exploring the efficacy of IVIg with this condition, it is believed that there are significant opportunities for patient symptoms to be alleviated by this treatment; however, additional studies are required to determine to prove this efficacy more effectively.14  The utilization of this treatment continues to expand for a wide variety of autoimmune diseases with serious inflammatory properties that are often difficult to manage in many patient populations, even though the complex nature of this treatment path is not easily understood.14

The utilization of IVIg treatment in patients is particularly useful in improving the immune response to protect tissues from further harm by disabling antibodies from performing their roles to reduce inflammation. 15 These properties demonstrate that IVIg provides a means of reducing inflammatory properties through its binding process, thereby reducing the ability of death receptors to bind to cells accordingly.15

The use of IVIg for autoimmune diseases of a neurological nature requires a greater understanding of the different elements which impact this use on a regular basis. Some researchers argue that the use of IVIg in this capacity is not yet fully explored, which may lead to problems in understanding the full capacity of this treatment method in treating neurologically-derived autoimmune disease.16  Under these circumstances, additional research is required to determine if this is the  optimal treatment choice for patients.¹⁶ Although this treatment has been proven effective in treating Guillian-Barre Syndrome, it is not necessarily as effective in treating other neurological autoimmune diseases.16  For some patient populations, IVIg is not always the most optimal treatment method on its own, but in combination with such treatments as prednisone in patients with Dermatomoysitis or Polymyositis at the appropriate stages, it is effective. 16  In addition, patients with a specific form of multiple sclerosis under certain conditions may benefit from IVIg treatments. 16 Under these conditions, it is expected that the condition may respond to this form of treatment, although the level of response may be reduced, thereby placing patients at a greater risk than was first anticipated.16 This requires clinicians to determine which alternatives are optimal for their patients, given the challenges that they face with high levels of inflammation and other problems.16

One interesting application of IVIg treatment is being considered for newborns in alleviating the symptoms of such autoimmune disorders as hemolytic disease of the newborn (HDN) and neonatal autoimmune thrombocytopenia (NAIT).17 This approach to conquering autoimmune disease in the newborn has not been proven effective on a widespread basis, and additional studies are required so that the approval of this treatment is extended to the newborn population.17  However, additional research is required to determine its efficacy and if any long-term damage could be sustained for newborns.17  Newborn patients may face difficult and potentially irreversible challenges associated with IVIg treatments and these circumstances should be examined carefully before any decisions are made regarding this treatment alternative.17  In addition, it is important to recognize that the use of IVIg treatment in newborns may lead to conditions such as necrotizing enterocolitis; therefore, extreme caution should be exercised when considering this treatment method. 17 Therefore, clinicians and researchers must exercise caution when considering IVIg for their newborn patients to minimize any potential damage that might occur.17

Finally, in exploring the benefits of IVIg further, it is important to recognize and tabulate the current conditions and other opportunities that are available to incorporate this treatment method for patients with autoimmune disease.  Clinicians must recognize the efficacy of this treatment plan and how to best treat autoimmune diseases given the history of this approach in treating these conditions. The following chart considers current disorders for which IVIg is used as a viable treatment method.

This chart provides additional evidence that IVIg is a viable and effective treatment method for use and applicability to a wide variety of autoimmune disorders, and that additional disorders might benefit from this treatment alternative with expanded research and clinical trials.18

These efforts are likely to produce a number of effective alternatives for patients with severe inflammatory responses that are too complex and unmanageable under some conditions.18 It is expected that this treatment regimen will also be evaluated in an expanded form for newborns who have been diagnosed with autoimmune disorders, as well as in evaluating their plasma for potential antibodies to produce the treatment itself.18 Each of these conditions is very likely to produce any number of important outcomes for patients within a number of different population groups to alleviate their inflammatory symptoms and other problems that may arise as a result of these autoimmune diseases. The nature of plasma in the newborn is essential to the discovery of new treatment methods and other factors which may effectively contribute to the immune response for patients who have been diagnosed with autoimmune disease. The impact of plasma generation and the extraction of antibodies to contribute to the IVig serum is likely to play a critical role in shaping how the treatment plan will take place and how patients will respond to this treatment regimen after repeated doses over a period of time, given other circumstances that may impact the effectiveness of this treatment strategy and how it may impact patient wellbeing and disease management.

Conclusion

The use of intravenous immune globulin (IVIg) in treating a variety of autoimmune disorders is a breakthrough of sorts in managing the symptoms of these conditions for those patients who are directly impacted by these events. The inflammatory properties of these conditions are often very difficult to manage and require a treatment regimen which supports effective long-term successful outcomes. Although there are potential side effects as with any type of treatment, it is nonetheless important to determine if this type of treatment method is appropriate for patients given their history of symptoms because it could be highly useful in treating autoimmune disorders with high inflammatory properties. Nonetheless, the treatment method must be successfully purified and maintained in order to improve the anti-inflammatory response of the treatment and to alleviate autoimmune-related symptoms in patients. This type of treatment approach has become increasingly common in treating autoimmune disease, even if its properties and pathophysiology are not clearly understood. With the ever-increasing presence of inflammatory conditions within all age groups, it is more important than ever to determine how to effectively provide treatment for these patients in order to improve the anti-inflammatory response as best as possible to these complex conditions that often attack organs and systems in different ways. Additional clinical studies must be performed to determine how to improve outcomes for patients who face a variety of autoimmune diseases with symptoms that are difficult to manage on a consistent basis. These studies may include a variety of treatment methods that could ultimately create an optimal immune response to the diagnosed condition. The development of an optimal treatment approach to manage autoimmune disease should always consider IVIg due to its overall safety and efficacy for a number of conditions for children and adults, in spite of its risks.  Future studies must also be identified that will also explore the efficacy of this treatment plan for newborns who have been diagnosed with autoimmune disease. These studies will further demonstrate the effectiveness of this treatment and the improved management of possible side effects or other risks that might occur as a result of this treatment method in patients from a variety of population groups. Although IVIg remains difficult to understand from a conceptual point of view, it is nonetheless one of the most important treatment alternatives for patients who face inflammatory diseases which attack the immune response. Therefore, this treatment method should always be considered in the context of its ability to fight disease and to create opportunities for expanded knowledge regarding the efficacy of treatments under these difficult conditions.

References

Gelfand EW. Intravenous immune globulin in autoimmune and inflammatory diseases. N Engl J Med. 2012;367:2015-25.

Quick A & Tandan R. Mechanisms of action of intravenous immunoglobulin in inflammatory muscle disease. Current Rheumatology Reports 2011;13(3):192-198.

Nimmerjahn F. & Ravetch, JV. Anti-inflammatory actions of intravenous immunoglobulin. Annual Review of Immunology.2008;26:513-533.

Jacob S & Rajabally YA. Current proposed mechanisms of action of intravenous immunoglobulins in inflammatory neuropathies. Curr Neuropharmacol. 2009 December; 7(4):337-342.

DurandyA, Kaveri SV, Kujipers, TW, Basta, M, Miescher, S, Ravetch JV & Rieben R. Intravenous immunoglobulins – understanding properties and mechanisms. Clin Exp Immunol. 2009 December. 158(Suppl 1):2-13.

Stanley JC, Toyoda M & Vo AA. Intravenous immunoglobulin a natural regulator of immunity and inflammation. Transplantation 15 July 2009;88(1):1-6.

Lux A, Aschermann S, Bilburger M, & Nimmerjahn F. The pro and anti-inflammatory activities of immunoglobulin G. Ann Rueum Dis 2010;69:i92-i96.

Lazarus AH. Adoptive-transfer effects of intravenous immunoglobulin in autoimmunity. J Clin Immunol. 2010;30(Suppl 1):S20-S23.

Stangel M, Baumann, U, Borte, M, Fasshauer, M, Hensel, M, Huscher, D, Kirch, W, Pittrow, D, Raiser, M, & Gold, R. Treatment of neurological autoimmune diseases with immunoglobulins: first insights from the prospective SIGNS registry. Journal of Clinical Immunology. Published online 14 September 2012.

Pithadia, AB & Kakadia, N. Guillain-Barre syndrome (GBS). Pharmacological Reports. 2010;62:220-232.

Caress JB, Kennedy BL, & Eickman, KD. Safety of intravenous immunoglobulin treatment. Informahealthcare. 2010;9(6):971-979.

Seite JF, Shoenfeld Y, Youinou P, & Hillion S. What is the contents of the magic draft IVIg? Autoimmunity Reviews. 2008;7:435-439.

Anthony RM, Wermeling F, Karlsson MI, & Ravetch JV. Identification of a receptor required for the anti-inflammatory activity of IVIG. PNAS.2008;105(50):19571-19578.

Rogosnitzky M, Danks, R, & Holt, D. Intravenous immunoglobulin for the treatment of Crohn’s disease. Autoimmunity Reviews.2012;1-6.

von Gunten S & Simon HU. Cell death modulation by intravenous immunoglobulin. Journal of Clin Immunology.2010;30(Suppl 1):24-30.

Elovaara I, Apostolski S, van Doorn P, Gilhus NE, Hietaharju A, Honkaniemi J, van Schaik N, Scolding N, Soelberg Sorensen P, & Udd B. EFNS guidelines for the use of intravenous immunoglobulin in treatment of neurological diseases. European Journal of Neurology. 2008;15:893-908.

Navarro M, Negre S, Golombek S, Matoses ML, and Vento M. Intravenous immune globulin: clinical applications in the newborn. Neoreviews. 2010;11(7):e370-e378.

Belderbos ME, Levy O, Meyaard L, & Bont L. Plasma-mediated immune suppression: a neonatal perspective. Pediatr Allergy Immunol 2012:1-12.