De novo natural anti-M alloantibody emergence in severe Coronavirus Disease 2019

Following Natural Autoantibodies: Further Immunoserological Evidence Regarding Their Silent Plasticity and Engagement in Immune Activation

“…Therefore, it can be considered a limitation of this study. Nevertheless, in accordance with previous articles cited throughout the present manuscript [1][2][3][4][5][6][13][14][15][16][48][49][50][79][80][81][82], the primary focus of our investigation was to suggest an immunologically acceptable, maybe even thought-provoking explanation for the herein-detailed empirical phenomenon, detected and experimentally proven at the level of immunoserological measurements.…”

“…To summarize, herein we present epidemiological and immunoserological data on associations between virus-specific "target" antibodies and "off-target" or "adventitious" nAAbs (Figure 8). Our observations are supplemented by a growing body of literature investigating potential connections between immunization and the concurrent dynamic change in the nAAb repertoire [13][14][15][16][32][33][34][35][36][37]. Based on our current findings, in case of a contemporary antigenic trigger, for SARS-CoV-2 vaccines, in terms of potential associations between virus-specific antibodies and "adventitious" nAAbs, statistically significant associations have been found in connection with the IgG isotype of nAAbs.…”

“…Some of these maintain that there is an elevated risk of vaccine-associated pathological auto-antibody formation [1][2][3], while others state that it is rather the natural infection being the major inducer of autoantibody formation [2,5,6], and that COVID-19 vaccines do not significantly foster the appearance of pathological autoantibodies commonly linked to the most prevalent autoimmune conditions [4]. Interestingly, the association between vaccination (or infection) and the non-pathological (natural) autoantibodies is much less studied [13][14][15][16].…”

“…Compared to the pathological ones, these non-pathological or nAAbs are much less studied. Although 2 of 19 they usually remain quiet, these fundamental participants in the immunological network feature some very important, yet unrecognized, physiological functions [9,[12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31].…”

“…These antibodies have moderate affinity, are typically poly-reactive, and their levels are physiological and thought to be relatively constant throughout life [9,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31]. However, in the modern literature, there is increasing evidence of the moderate inducibility of the nAAb repertoire [13][14][15][16][32][33][34][35][36][37].…”