Time to put Kir4.1 as a major autoimmune target to bed...it isn't

Pröbstel AK, Kuhle J, Lecourt AC, Vock I, Sanderson NS, Kappos L, Derfuss T. Multiple Sclerosis and Antibodies against KIR4.1. N Engl J Med. 374:1496-8.

Chastre A, Hafler DA, O'Connor KC. Evaluation of KIR4.1 as an Immune Target in Multiple Sclerosis. N Engl J Med. 2016 14;374(15):1495-6.

The search for specific autoantibodies in patients with multiple sclerosis has been an area of intensive research for decades, but the unequivocal identification of one or several autoantigens associated with the disease has remained elusive. 

However, considerable interest has been raised by a study showing the presence of serum autoantibodies to KIR4.1, an astrocytic inward-rectifying potassium channel, in 47% of adult patients with multiple sclerosis but not in patients with other neurologic diseases or in healthy controls. 

However, subsequent independent studies that were performed with the use of a cell-based assay or peptide antigen–based enzyme-linked immunosorbent assay (ELISA) have not corroborated these findings..

On study tested the original method used with 141 pwMS and 131 controls and got nothing interesting.

In the other study a commonality among the studies that have contradicted the original report is that one of the three approaches that were originally used to measure the autoantibodies, a protein antigen–based ELISA, was not used. 

Here the other study made the channel which contains four subunits and had a positive control and then tested the activity in 86 pwMS......No difference for most people..end of story. 

There experiences found technical challenges methodologies but suggest that people doing these types of study should create replicate samples, that can be provided for replicate experiments by totally independent groups. Then we will more quickly dissect fact from fiction.

How come two papers arise at the same time, either they were talking to each other after one showed the data and the other said hey we have the same data, or maybe one was reviewing the other and said hey we have the same data. However two more agreements and the original data seems more and more on thin ice.