Newborn blood spot test extended to detect more than 50 immunodeficiencies

By Roseli Andrion  |  FAPESP Innovative R&D – Some 2.5 million babies are born in Brazil every year. Each one is submitted to neonatal screening to detect serious congenital diseases so they can be treated early. Known as the newborn blood spot test or heel prick test, the procedure has been performed in Brazil since the 1970s and was made compulsory in 1992. It is fast, non-invasive and practically painless. Public and private hospitals alike perform it. Birth certificates cannot be issued without it.

The newborn blood spot test can detect more than 50 immunodeficiencies, although most hospitals in Brazil still perform a limited version that detects only six. A law passed in 2021 requires all health services nationwide to offer the extended version of the test by 2026.

With support from FAPESP’s Innovative Research in Small Business Program (PIPE), Immunogenic, a health tech startup based in São Paulo city, has developed a test that recognizes more than 50 primary immunodeficiency diseases. Research to develop an extended indigenous neonatal screening alternative began in 2009 at the Jeffrey Modell Center Brazil, involving validation in thousands of samples. “The aim is to identify rare immunodeficiencies,” says immunologist Antonio Condino-Neto, medical director of the startup and a professor at the University of São Paulo’s Biomedical Sciences Institute (ICB-USP).

According to Condino-Neto, treatments for some of these rare diseases have been developed thanks to the advance of technology. “It only makes sense to detect them by neonatal screening if treatment exists. You create this option if the incidence of the disease is significant and if it can be treated. It’s for conditions that must be diagnosed early. There’s little sense in diagnosing one of these diseases once it’s already happened,” he says.

Immunodeficiencies meet all these criteria. The earlier the diagnosis, the better, in every case. “Severe combined immunodeficiency [SCID], for example, should ideally be diagnosed in the first month of a baby’s life. The treatment begins with genotyping. A stem cell transplant can be scheduled before the end of the third month,” Condino-Neto says.

According to him, there are about 20 forms of SCID, all of which are detected by Immunogenic’s test kit. “A baby with agammaglobulinemia lacks mature B lymphocytes and is born with antibodies received from the mother during her pregnancy, but by the sixth month of life no longer has them and can’t produce anymore. Early diagnosis prevents death before the baby’s first birthday. Immunoglobulin replacement is covered by the SUS [Sistema Único de Saúde, Brazil’s public healthcare network], as are other treatments for immunodeficiencies,” he explains.

Brazilian hospitals currently use imported kits to perform the neonatal screening test for these diseases. Immunogenic’s scientists have developed an indigenous solution based on academic research. “This has direct application to healthcare for the individual and we couldn’t continue in an academic laboratory, so we founded Immunogenic,” Condino-Neto says. “The startup is almost a copy of ICB-USP’s human immunology lab but offers products for the market.”

Search for partners

Immunogenic’s test kit is already used by Jô Clemente Institute, a disability services and support organization formerly called APAE São Paulo. A 2020 law requires performance of the extended test in São Paulo city. “In two years, with an average of 8,000-10,000 tests per month, we diagnosed eight cases of SCID: two cases of congenital agammaglobulinemia and the first case of congenital leukemia in the world,” he recalls. “Statistically speaking, we identified twice the expected number. That makes us feel very excited.”

Next steps will be registration of the test with ANVISA (Brazil’s regulator of healthcare procedures, medical drugs and devices), and a search for partners to make it. “A locally produced kit will have the advantage of being cheaper. It will also be the outcome of 15 years of research, sensitivity calibration [to minimize false negatives] and fine-tuning of specificity [to minimize false positives] for Brazilian DNA,” he says.

Imported test kits are not sensitive to everything detected by locally produced ones. “They’re good tests but we’ve spent 15 years calibrating ours for Brazilian DNA, which is different from other countries’ DNA. Our kit even diagnoses spinal muscular atrophy [SMA],” he says.

The team is currently studying the main competitor of its test. “Information from a catalog is one thing; real life is quite another,” he says. Moreover, standardization of the process based on thousands of samples is needed for neonatal screening to be effective. “The imported test comes with instructions for the user to do their own normality curve. We’ve worked on this for 15 years and provide more precise parameters. Even so, each Brazilian state will have different references, and everything will have to be redone if there’s a change of platform.”

The indigenous test has another advantage: it is compatible with any type of molecular biology equipment, whereas its competitors require proprietary equipment to be purchased to process samples. “Our test can be used anywhere in the world – it has that flexibility,” he says.

In fact, Immunogenic is seeking prospective buyers of its test kit in other countries. “Negotiations to sell our test into other markets are already at an advanced stage,” he says. “It can be used in Europe, the United States, Africa, Asia, Oceania, everywhere. Users in other countries will have to reconfirm our reference with their own samples, but that’s not a drawback because the solution is flexible as far as processing platforms are concerned. Also, it will cost half the price of the competition, if not even less.”

The extended neonatal screening test is available in few places without additional cost. “It's guaranteed for all babies born in public hospitals in São Paulo city, but users should check whether the option is available in the rest of the state and everywhere else. It hasn’t yet been included in the list of mandatory procedures by the National Supplementary Health Agency [ANS], so it isn’t covered by health insurance plans,” he says.

For Condino-Neto, the test will only be listed by ANS if society demands it, which requires education to raise awareness and bring pressure to bear on the authorities. “Once that happens, coverage by medical plans will be mandatory. They represent more or less 30% of the market in Brazil. That’s a significant share and coverage by the private sector will lessen the burden for the SUS,” he says.

Childbirth involves needs of mother and baby, and both should be satisfied, he adds: “It’s important for the mother to be able to give birth in healthy conditions and without complications, and for the baby to undergo the complete newborn screening test. That’s what we want.”

(image from Pixabay)