Coeliac disease, mucosal change and IEL: doing what counts the best.

There has been a flurry of activity in GHFBB arising from my classification (1), and I am flattered that the editors have now asked me for an overview. Readers should note that the flurry originated from a recent paper (2) in which we revealed the redundancy of Oberhuber's re-classification of the Marsh III coeliac lesion. First, we indicated that there is no structural basis for his assertion. Second, there is a need to recognise that his subdivisions have never offered useful contributions either to diagnosis, response to treatment, or longer-term outlook. So why use them? And, for those who had the initiative to enquire, no correspondence exists between Oberhuber's subdivisions (despite their technically poor quality) and those of others (3), despite both being offered as supportive guides for histopathologists. That observation emphasises the subjectivity of the exercise. But that revelation hardly surprises, since no structural criteria were ever produced to guarantee reproducibly standard sub-classifications. That is the impasse, but one which is easily bypassed. The flurry of editorials and correspondence gave rise to a completely different focus, unfortunately, from that intended in our paper. That outcome asked an entirely different question: which classification is the best? No answer emerged. What to me matters is that histopathologists (most likely through pattern recognition) can spot the infiltrated lesions of Marsh I and Marsh II, as well as a flat lesion (Marsh III) in comparison with "normal" (Marsh O). For university-educated people, is that too much for them to hold in their brains? What real value obtains by reducing those simple precepts? Let me elucidate. First, however, some preliminaries need to be aired as foundational for this review. My paper in Gastroenterology (1992) was an attempt to entice the pursuit of "coeliac disease" out of the doldrums of its c1950-oriented thinking and practice, and catapult it into the molecular world of the 21 st Century (1). That involved bringing together all the known sequences of the gliadins and cognate proteins as a first step towards predicting likely immunogenic epitopes, and secondly, considering possible polymorphisms in the HLA genes of those sensitised to gluten. Next, I suggested that the coeliac-associated lymphomas should be tabulated and classified. We now have two internationally-acclaimed units (at least) in Paris and Amsterdam which have achieved that aim with distinction. Fourthly, I had also realised, as hinted at sporadically in the literature, that there was a spectrum of mucosal …