The goal

What did scientists want to find out?

PNH is almost always caused by a mutation in the PIGA genegenesSections of our DNA that act as our body’s instruction manual. Each person has two copies of each gene, one inherited from each parent. They determine our characteristics and traits, including physical characteristics like eye and hair color. Some genes can be responsible for disease.. This gene is required to synthesize cell components called GPI protein anchors. These anchors act like hooks, helping key proteins to attach to red blood cellsred blood cellsThe most common type of blood cell. Their job is to carry oxygen using an important molecule, hemoglobin, around the body. and protect them from being destroyed by the immune systemimmune systemA sophisticated defense network used to protect the body from dangers like disease and infection..

In this study, scientists explored a different type of PNH. It may be caused by another gene, PIGT. The scientists set out to describe the differences between PNH caused by PIGT and PNH caused by PIGA.

The method

How, where and when did they look for information to analyze?

In PNH caused by PIG-A, the bone marrow never makes the GPI protein anchors. Since the GPI protein anchors are missing from the cell surface, the protein has no way to attach to the cell.

  • In PNH caused by PIG-T, cells do have GPI protein anchors — but no attached protein.

The authors of the study evaluated and described 4 people whose PNH arose from the PIG-T gene.

  • To have this form of PNH, an individual must have an extremely rare combination of 2 genetic mutations: one that occurs before birth, called a germline mutation, and another that occurs when a section of chromosome 20q is randomly deleted. This is a specific chromosome that provides instructions for the body to create a number of important proteins.

The findings

What did the researchers learn?

People who have PIG-T PNH may have more inflammatory symptoms, including aseptic meningitis, or inflammation of the brain’s lining; recurring hives; and joint pain.

These symptoms can appear years before the person develops PNH.

The takeaway

What did the researchers conclude from the study?

  • The researchers concluded that subtle but important factors make PNH resulting from PIGA different from PIGT. These differences suggest that PIGT PNH may be its own distinct disease — even rarer than PNH (which occurs in about one in a million people each year). People with PIGT PNH make up less than 1 percent of people with PNH. They may respond well to available PNH treatments
  • For doctors, it is important to consider GPI-anchored protein deficiency due to PIGT mutations for individuals with recurrent autoinflammatory symptoms — even when PNH symptoms are absent. Inhibiting the immune system may help manage these cases
Please note: The information on this page is meant to be informational only and is not intended to replace medical advice. Always talk to your healthcare provider about any questions you may have on PNH, its symptoms or treatment.
  • Title: Commentary: Paroxysmal nocturnal hemoglobinuria without GPI-anchor deficiency
  • Journal: Journal of Clinical Investigation 2019;129(12):5074-5076
  • Written by: Brodsky R. A.