Aswini B | 21 January 2020
Our immune system is an army, with the immune cell warriors spread throughout our body for constant check out for invading microbes and allergens to fight against and guard us. When the function of the immune system is disrupted, our body is open for incursion by microbes and is prone to multiple diseases. Defects in the development or maturation or function of the immune system result in a heterogeneous group of over 330 immune disorders. They are called primary immunodeficiency (PID). The primary immunodeficiency disorders are rare. They encompass a spectrum of Mendelian genetic disorders caused by mutations in the genes that are responsible for the development and maturation of immune cells. The International Union of Immunological Societies (IUIS)(Bousfiha et al., 2018) has classified PID into nine classes, based on the affected cell type.
It is estimated that more than 6 million individuals are affected by primary immunodeficiency disorders globally. Although we do not have the exact prevalence of the disorders in India, Asia has the largest share of affected individuals (Jindal et al., 2017). Dysregulation of the immune system manifests variable clinical symptoms. Hence, to spread awareness among the public and clinicians, the Jeffrey Modell Foundation has classified ten distinct warning signs for primary immunodeficient patients. The common symptoms for PID patients are recurrent bacterial, viral or fungal infections, persistent thrush, recurrent pneumonia, growth delay, very little or no effect of antibiotics, and family history of PID. An adapted version of these warning signs pertinent to Indian settings has also been created, to aid clinician and patient awareness and diagnosis.
Primary immunodeficiency is a critical condition and requires proper attention and care. The patient must be educated about the crucial details of the condition and their health. It will help them to decide why and what kind of lifestyle changes they should develop. Patient education, along with improving the understanding of the medical condition, also aids in reducing patient anxiety and deal with methods to manage the condition.
Accurate diagnosis of primary immunodeficiency is challenging for clinicians due to the overlapping symptoms. Hence, precise education of the disorder is crucial for both patients and clinicians. Handbooks for clinicians and patients are available in this regard.
Apart from the high clinical suspicion, a variety of tests are used to diagnose patients suffering from Primary immunodeficiency disorder These tests could be as simple as complete blood count (CBC), but in many cases, one would require advanced methods like flow cytometry, antibody level estimation dihydrorhodamine (DHR), stimulation assay, and Gene Sequencing.
In many developed countries, newborn screening programmes for severe combined immunodeficiency (SCID) and T/B cell immunodeficiencies have been established using a unique assay which relies on the circular DNA isoforms produced during the maturation of T and B cells. These assays- T cell receptor excision circle (TREC) assay and kappa-deleting recombination excision circle (KREC) assay offers a highly sensitive screen to identify children with Primary immunodeficiency disorders and enable their early treatment.
With the expanding number of genes being discovered, next-generation sequencing (NGS) is increasingly being used to establish a molecular diagnosis. Early diagnosis is crucial for explicit care and management of the patient. But the cost of these diagnostic methods is too high, making it unaffordable for the patients.
Under the Genomics for Understanding Rare Disease India Alliance Network (GUaRDIAN) programme at CSIR-IGIB, a large cohort of patients have been created, in collaboration with the Government Medical College Kozhikode. A genomics approach has been employed to sequence a large number of patients suspected to have a primary immunodeficiency disorder (Find more about the research here). This has enabled us to identify a subset of diseases which are prevalent in the population and have specific genetic variations which recur in patients. This opens up an opportunity to develop cost-effective genetic diagnostics.
The Government Medical College Kozhikode today operates a specific clinic for patients suffering from Primary immunodeficiency disorders. The clinic offers patients comprehensive care, genetic testing, and counselling. Several patients are currently under treatment, supported by the government of Kerala. It is also heartening to note that a few patients could be provided Haematopoetic Stem Cell transplants - therefore providing a definitive cure to the condition.
Going forward, the number of centres offering patient care and genomic diagnosis under the GUaRDIAN programme has gone up and now covers major centres in Delhi, Maharashtra, and Gujarat. A cost-effective screening test based on the TREC and KREC assays are being developed to enable fast screening of children and is hoped to enable the screening and accurate diagnosis of many more patients. Besides, cost-effective genetic tests are now being implemented in the collaborating centres for diseases prevalent in the region.
To educate patients and caregivers, the programme has also been organising specialised education programmes. The first meeting on primary Immunodeficiency disorders - CUREPID was organised at Government Medical College, Kozhikode. Patient information material in vernacular languages, as well as a handbook for clinician education, is also made available through the programme.
The programme is currently inviting clinicians and collaborators in an attempt to benefit more people across the country. Clinicians, who would be interested in referring a case, or interested in setting up a local node for primary immunodeficiency disorders in their medical college/hospital could reach out to us directly.
Find more about the GUaRDIAN programme on Primary Immunodeficiency Disorders at http://is.gd/pidindia
Our immune system is an army, with the immune cell warriors spread throughout our body for constant check out for invading microbes and allergens to fight against and guard us. When the function of the immune system is disrupted, our body is open for incursion by microbes and is prone to multiple diseases. Defects in the development or maturation or function of the immune system result in a heterogeneous group of over 330 immune disorders. They are called primary immunodeficiency (PID). The primary immunodeficiency disorders are rare. They encompass a spectrum of Mendelian genetic disorders caused by mutations in the genes that are responsible for the development and maturation of immune cells. The International Union of Immunological Societies (IUIS)(Bousfiha et al., 2018) has classified PID into nine classes, based on the affected cell type.
It is estimated that more than 6 million individuals are affected by primary immunodeficiency disorders globally. Although we do not have the exact prevalence of the disorders in India, Asia has the largest share of affected individuals (Jindal et al., 2017). Dysregulation of the immune system manifests variable clinical symptoms. Hence, to spread awareness among the public and clinicians, the Jeffrey Modell Foundation has classified ten distinct warning signs for primary immunodeficient patients. The common symptoms for PID patients are recurrent bacterial, viral or fungal infections, persistent thrush, recurrent pneumonia, growth delay, very little or no effect of antibiotics, and family history of PID. An adapted version of these warning signs pertinent to Indian settings has also been created, to aid clinician and patient awareness and diagnosis.
Primary immunodeficiency is a critical condition and requires proper attention and care. The patient must be educated about the crucial details of the condition and their health. It will help them to decide why and what kind of lifestyle changes they should develop. Patient education, along with improving the understanding of the medical condition, also aids in reducing patient anxiety and deal with methods to manage the condition.
Accurate diagnosis of primary immunodeficiency is challenging for clinicians due to the overlapping symptoms. Hence, precise education of the disorder is crucial for both patients and clinicians. Handbooks for clinicians and patients are available in this regard.
Apart from the high clinical suspicion, a variety of tests are used to diagnose patients suffering from Primary immunodeficiency disorder These tests could be as simple as complete blood count (CBC), but in many cases, one would require advanced methods like flow cytometry, antibody level estimation dihydrorhodamine (DHR), stimulation assay, and Gene Sequencing.
In many developed countries, newborn screening programmes for severe combined immunodeficiency (SCID) and T/B cell immunodeficiencies have been established using a unique assay which relies on the circular DNA isoforms produced during the maturation of T and B cells. These assays- T cell receptor excision circle (TREC) assay and kappa-deleting recombination excision circle (KREC) assay offers a highly sensitive screen to identify children with Primary immunodeficiency disorders and enable their early treatment.
With the expanding number of genes being discovered, next-generation sequencing (NGS) is increasingly being used to establish a molecular diagnosis. Early diagnosis is crucial for explicit care and management of the patient. But the cost of these diagnostic methods is too high, making it unaffordable for the patients.
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| Abhinav Jain, Graduate Student at CSIR Institute of Genomics and Integrative Biology explores the application of Genomics in Primary Immunodeficiency Disorders. |
Under the Genomics for Understanding Rare Disease India Alliance Network (GUaRDIAN) programme at CSIR-IGIB, a large cohort of patients have been created, in collaboration with the Government Medical College Kozhikode. A genomics approach has been employed to sequence a large number of patients suspected to have a primary immunodeficiency disorder (Find more about the research here). This has enabled us to identify a subset of diseases which are prevalent in the population and have specific genetic variations which recur in patients. This opens up an opportunity to develop cost-effective genetic diagnostics.
The Government Medical College Kozhikode today operates a specific clinic for patients suffering from Primary immunodeficiency disorders. The clinic offers patients comprehensive care, genetic testing, and counselling. Several patients are currently under treatment, supported by the government of Kerala. It is also heartening to note that a few patients could be provided Haematopoetic Stem Cell transplants - therefore providing a definitive cure to the condition.
Going forward, the number of centres offering patient care and genomic diagnosis under the GUaRDIAN programme has gone up and now covers major centres in Delhi, Maharashtra, and Gujarat. A cost-effective screening test based on the TREC and KREC assays are being developed to enable fast screening of children and is hoped to enable the screening and accurate diagnosis of many more patients. Besides, cost-effective genetic tests are now being implemented in the collaborating centres for diseases prevalent in the region.
To educate patients and caregivers, the programme has also been organising specialised education programmes. The first meeting on primary Immunodeficiency disorders - CUREPID was organised at Government Medical College, Kozhikode. Patient information material in vernacular languages, as well as a handbook for clinician education, is also made available through the programme.
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The programme is currently inviting clinicians and collaborators in an attempt to benefit more people across the country. Clinicians, who would be interested in referring a case, or interested in setting up a local node for primary immunodeficiency disorders in their medical college/hospital could reach out to us directly.
Find more about the GUaRDIAN programme on Primary Immunodeficiency Disorders at http://is.gd/pidindia
References:
Bousfiha, A., Jeddane, L., Picard, C., Ailal, F., Gaspar, H.B., Al-Herz, W., Chatila, T., Crow, Y.J., Cunningham-Rundles, C., and Etzioni, A. (2018).
The 2017 IUIS phenotypic classification for primary immunodeficiencies.
Journal of Clinical Immunology 38, 129-143.
Jindal, A.K., Pilania, R.K., Rawat, A., and Singh, S. (2017).
Jindal, A.K., Pilania, R.K., Rawat, A., and Singh, S. (2017).
Primary immunodeficiency Disorders in India—A situational review.
Frontiers in Immunology 8, 714.