Often, one hears about harrowing experiences of parents rushing from pillar to post to get 'proper' care for their children suffering from infections that refuse to go away, often resulting in the tragic loss of life. Few people suspect these recurring infections are caused by weakened immune systems, many of which are classified as rare diseases.

However, though called rare diseases, considering their prevalence, rare diseases are not very rare, says Prof Sudhir Gupta of the University of California, and urges the government to take up the issue of treating rare immunological diseases as a priority.  

Professor Sudhir Gupta, a well-known academician and researcher in the field of immunology, obtained his MD and PhD from Lucknow University. His research interests include Molecular signalling of apoptosis, Dendritic cell biology, B cell biology, and the genetic basis of primary immunodeficiency diseases.

Prof Gupta, a man of intellect, has received numerous academic honours, including the Arthur Manzel Research Award and the Lifetime Achievement Award from Jeffery Modell Foundation.

He was a member of the NIA's Cellular Mechanisms of Aging and Development Study Section from 2003 to 2008. He is now a member of the NIA's Aging Systems Gerontology Study Section since 2008.

Prof Gupta is currently the Director of the Jeffrey Modell Diagnostic Center for Primary Immunodeficiencies and the Chief of Basic and Clinical Immunology at the University of California, Irvine, and is the President of the Foundation for Primary Immunodeficiency Disease.

Prof Gupta spoke to Drug Today Medical Times’ Rohit Shishodia during his recent visit to India for the three-day 6th International Conference on Inborn Errors of Immunity in Gurugram, Haryana, on several topics, including the role of immunology in disease management and diagnosis.

DTMT: Please give our readers some insight about the conference.

Prof Gupta: This international conference is an annual event that deals with children born with genetic defects of the immune system, which makes them very susceptible to serious and life-threatening infections.

If the underlying causes are not recognised early, the children may die of infections, and nobody will ever know what happened.

This conference discusses all the major advances achieved in the field, the current work that is underway and what the future holds for us. Here, we had 11 speakers from abroad, including speakers from the United Kingdom, the United States, Australia, and Italy, who have discovered some of these diseases, and several delegates and speakers from India.

In the last ten years, India has vastly transformed concerning awareness of these diseases, diagnosis, and treatment.

The treatment includes giving infusions of antibodies that the patients lack, which makes them susceptible to infection, as well as performing bone marrow transplants because these children are born without an immune system and an immune system is what keeps us healthy.

So those are the advances in the last ten years before which there was no awareness in India, and now they can make the diagnosis as early as 18 weeks of pregnancy. So India has come a long way but still has to cover a lot because treatments are expensive, they are not available to everyone and that is where the government needs to step in.

They always think that these are rare diseases, so this is not their priority. I am working with the government, secretary of health research as well as ICMR in that direction.

I run a charitable foundation in the United States, primarily supporting these activities in India, which started eleven years back. We have eight centres spread across the country, including PGI-Chandigarh, Mumbai, Calicut, Bengaluru, Hyderabad, JNI-Puducherry and SGPGI-Lucknow. Over 120 researchers presented their work during the conference.

DTMT: From the layman’s perspective, there are diseases that parents do not know what their children suffer from. What will be your message to doctors and parents?

Prof Gupta:  The message is to be suspicious of these terrible infections since children will die if they are not recognised and treated for severe infection. So, if children have repeated severe infections in their early childhood that necessitate hospitalisation, one should think that they may be suffering from these disorders and should visit specialists.

And if they (these doctors) do fail to recognise them, then there are eight centres across the country for diagnosis and the treatment of these diseases because each disease of the weakness of the immune system may be very rare, but there are about 485 different diseases of the weakness of the immune system.  

When they are combined, they become a common lot, so they are not rare, but it is the public's awareness and education for general practitioners and paediatricians that matters.

In these eight centres, which have developed over the ten years, one of their functions is to do the CME course for community physicians, including ENT specialists, because these patients can develop a lot of sinus infections and they can develop pneumonia too, so they do not respond appropriately to antibiotics.

So with antibiotics, they get better, but infections recur, and such kids never get cured with antibiotics.

DTMT: Tell our readers which diseases are not commonly diagnosed.

Prof Gupta:  As I told you there are 485 different diseases, but the common thing is that their immune system is not making antibodies to fight bacterial infections or other parts of the immune system that fight viruses, fungi and also cancer.

So when you have a weakness in the immune system, they can come to their primary doctor who can be a physician or paediatrician. They can come with pneumonia and recurrent abscesses in the skin.

Some of them will come with autoimmune diseases such as rheumatoid arthritis; lupus and they may have these diseases to begin with.

Whenever you have a severe form of disease very early in life always think about the fact that they have a primary defect in your immune system and just go to these centres.

DTMT: As a specialist in the field of immunology can you please tell our readers how immunology medications are evolving in recent years?

Prof Gupta:  We can divide immunological medications into different categories. One, if you are deficient, for example in the antibodies we give antibodies as an infusion. Then there are other medications because knowing how that immune system is defective we can give some so-called biologics or a very targeted drug so they will affect that component or that function of the immune cells.

Thirdly, what is evolving is and has been there because they are missing or defective immune systems, and the immune system resides in the bone marrow or the glands, so if you do the bone marrow transplantation, you deal with the root cause leading to their getting cured.

We had only one centre ten years ago for treating uncommon disorders through bone marrow transplants. We now have 15-20 locations where bone marrow transplants can be performed.

 Another development that is taking place in so-called gene therapy. If a faulty gene is causing the sickness, you harvest their stem cells and insert the good gene before returning them to the patient. It is a  straightforward procedure because it is similar to administering an infusion, but outside you must inject the repaired gene.

 Again that is a random process, so there is another thing that is evolving, which we call gene editing. Here the part of the defective gene is cut just like by using scissors and inter the corrected one. It's a lot more precise. You don't know how much gene therapy is going on here and there, and you're modifying the gene. So those are some of the latest developments.

DTMT: Can you please tell our readers what lifestyle changes people should adopt to minimize the risks of autoimmune diseases?

Prof Gupta:  Autoimmune disease is something that you really cannot avoid. There are genes which make you susceptible to autoimmune diseases. So prevention is difficult because we do not know what exactly precipitates those autoimmune diseases.

There are several autoimmune diseases like thyroid. Five per cent of women are suffering from thyroid malfunction. So you give hormones to control them because thyroid glands won't function very well, which is the treatment. You have children born with diabetes, where the pancreas is not making insulin, and you give insulin. So in autoimmune diseases, we know there are certain mechanisms. So let's say the cell that makes antibodies,  we can treat it very effectively and remove those cells. So we have biologics that will defeat those cells that make autoantibodies. We cannot prevent the disease, but we can treat it very effectively.

DTMT: What are the challenges you find in India for managing and treating rare diseases, and what will be your advice to the Government of India?

Prof Gupta: The most important thing is unless the government takes them seriously as a health priority because they will always say this is not our priority, these are not common diseases. 

Even if one can save a few lives, it will be a great achievement, as every life is important! Who knows if one of them can become Mr Modi, for example, in future? 

Major obstacles come because all these approaches are costly, whether you do the bone marrow transplants, or use the biologics which are making antibodies, arrange availability and the procurement of those drugs, and the facility for bone marrow transplants, setting up infrastructures for gene therapy and gene editing are very important. Though they are not going to happen overnight, the government should have designated centres where these treatments can be done, and they should support this.