Study Finds High Rate of Children With Antibody-induced aHUS in Egypt
About four in 10 children in Egypt who have atypical hemolytic uremic syndrome (aHUS) test positive for antibodies against the complement protein factor H, a study has found.
These findings highlight the importance of testing for the presence of these antibodies to ensure prompt diagnosis and treatment, according to the researchers.
The study, “Anti-Factor H Antibodies in Egyptian Children with Hemolytic Uremic Syndrome,” was published in the International Journal of Nephrology.
aHUS is caused by the overactivation of a part of the immune system called the complement cascade, leading to blood vessel inflammation. In most cases, genetic mutations in complement genes — most commonly the gene encoding factor H, a complement regulator protein — help trigger the disease’s onset.
More rarely, aHUS can be caused by antibodies made by the immune system that erroneously bind and inactivate complement regulator proteins. This is called autoimmune aHUS, or AI-HUS. Antibodies targeting factor H, referred to as anti-FH, are the most common cause of AI-HUS.
“The identification of aHUS patients with anti-FH is important to target these patients with proper therapy, predict organ involvement, monitor relapses, guide appropriate follow-up, and adjust treatment accordingly,” the researchers wrote.
In the new study, the scientists, in Egypt and Japan, described clinical data for 28 children with aHUS treated at a center in Egypt. Data on 22 children with typical HUS was also reported.
“We aimed at studying the frequency of anti-FH as a contributing factor for the development of aHUS in Egyptian children and to explore its relation to disease severity and outcome,” the team wrote. “To our knowledge, this is the first study to test for the presence of anti-FHs in HUS patients in Egypt.”
Among the 28 aHUS patients, 12 (42.9%) were positive for anti-FH. This frequency was markedly higher than that reported in European aHUS groups, where anti-FH-positive rates have usually ranged between 5%–25%.
“Egypt potentially has one of the highest reported frequencies of AI-HUS,” the team wrote.
The most common aHUS symptoms were similar regardless of anti-FH status, and included diarrhea, vomiting, and fever.
Those who tested positive for the anti-FH antibodies were significantly older (mean of 7.7 vs. 4.3 years), and a greater proportion were male (83.3% vs. 37.5%).
The majority of anti-FH-positive patients (58.3%) experienced disease onset in the months of March or April, which was not seen for those lacking these antibodies. This may be because seasonal infections can help trigger anti-FH-mediated aHUS, the researchers noted.
Laboratory tests also revealed that patients who tested positive for anti-FH had significantly lower levels of platelets — cell fragments that are important for blood clotting — and significantly higher levels of lactate dehydrogenase, a marker of tissue damage, compared with anti-FH-negative patients.
Treatment and clinical outcomes generally were similar regardless of anti-FH status. Anti-FH-positive patients tended to respond better when treatment was initiated earlier on in the course of the disease, emphasizing the importance of a prompt diagnosis, the researchers wrote.
“We highlight the importance of the rapid detection of anti-FH and make the assay readily available for children with aHUS, especially older ones,” the investigators wrote. “The proper diagnosis of AI-HUS and rapid initiation of appropriate treatment will give the patients the chance of escaping renal injury, relapses, and attaining better outcomes.”
This study was limited by its small sample size, the fact that it was conducted at a single institution, and that anti-FH levels were measured only at a single point in time.
“Including a larger number of patients in a multicenter study and for longer periods of follow-up will help obtain detailed information about the occurrence of AI-HUS in Egypt and so better guidelines for management and consequent follow-up in these patients can be generated,” the researchers wrote.