In fact, although anti-Ro/SSA-antibodies alone cannot usually prolong QTc in a so critical manner to induce TdP development (similarly to all the other better recognized determinants of LQTS) (91, 94), nevertheless they can reduce the ventricular repolarisation reserve (92), thereby enhancing the arrhythmic risk when other conventional QT-prolonging factors (drugs, electrolyte imbalances, genetic mutations, etc.)are concomitantly present (multi-hit theory) (Figure 2) (24, 91, 95–99). Here, CALR is linked to familial long QT syndrome.