Is the Next Generation Sicker at a Younger Age?
Familial autoimmunity in the next generation may appear sooner and be more severe.
This is the very last study in my investigation of Multiple autoimmune syndrome (MAS). There are still unanswered questions to explore, such as: Why are psychological factors “implicated in the development of MAS”? What’s the meaning of the term “Autoimmune Tautology?” What are “Overlap Syndromes?” Are the tests used in New Insights… and Whole Exome Sequencing clinically useful outside of medical research at this time? Are they available? I’ll explore these questions, and summarize the science to date on Multiple autoimmune syndrome, in my next post.
Carrying on the theme of familial clustering of autoimmune disease, this 2011 Italian study characterizes disease prevalence in the relatives of younger (3-32 years of age) participants with Multiple autoimmune syndrome. This study explores familial autoimmunity in participants with a presenting autoimmune disease of Type 1 diabetes, Autoimmune thyroid disease, and Celiac disease.
Area of Investigation
Multiple Autoimmune Syndrome: when one person meets the study classification criteria for three or more autoimmune diseases.
Study Title
Intergenerational anticipation of disease onset in people with multiple autoimmune syndrome
Results
30 participants with polyautoimmunity and Multiple autoimmune syndrome were included in this study. That’s a very small sample size, so the applicability of the findings of this study are limited. With that caveat in mind, this study’s findings are still quite interesting.
At times, the authors incorrectly characterize all 30 participants as having Multiple autoimmune syndrome, but the chart below indicates that 18 participants have polyautoimmunity (two or more autoimmune diseases) and 12 participants have Multiple autoimmune syndrome (three or more autoimmune diseases). 28 out of the 30 study participants had at least one relative with an autoimmune disease. Inclusion criteria for the participants, and their relatives, was based on clinical/hospital histories and is not fully described in the publication. 52 relatives, out of 333 relatives assessed for autoimmune disease from “previous generations,” were identified as having at least one autoimmune disease, and included in this study.
Of the three index diseases studied (Type 1 diabetes, Autoimmune thyroid disease and Celiac disease) Type 1 diabetes was the most common, occurring in 23 (77%) out of 30 participants.
20 (74%) study participants, out of the 28 participants with polyautoimmunity/Multiple autoimmune syndrome and familial autoimmunity, had family members with the same autoimmune disease. 39.1% of 20 participants shared the diagnosis of Autoimmune thyroid disease with a relative from a previous generation. 34.7% of 20 participants shared the diagnosis of Type 1 diabetes. 17.3% of 20 participants shared the diagnosis of Celiac disease. 8.6% of 20 participants shared the diagnosis of psoriasis. It’s important to remember that out of 20 participants, these percentages represent a very small number of participants.
The following is the most interesting finding of this study. When the authors compared the age of onset of all of the diseases together, they found that the “mean age of disease onset was always significantly lower” in the younger generation compared to the older generation. Mean age of onset of the younger generation was 8.9 years +/- 5.7 years. Mean age of onset of the older generation was 28.8 years +/- 11.5 years. They found that the same was true when they considered age of onset of each individual disease: the mean age of onset was always significantly lower in the younger generation compared to the older generation.
Could this be the case because diagnostics have improved over time? Or that a definitive diagnosis in the older generation created an earlier suspicion for the same disease in the younger generation? The authors address these points by arguing that their study included easily recognized diseases that determined age of onset according to “overt clinical signs.” They also note that they “observed a more severe clinical phenotype,” otherwise known as signs and symptoms of disease, in the younger generation, “suggesting the worsening of the phenotype generation by generation.” They note that study selection bias could be responsible for this finding.
Why it Matters
Characterizing the genetic inheritability of autoimmune diseases is critical, because it increases the likelihood of symptom recognition and vigilance, aids in diagnosis, helps to identify the underlying mechanisms of disease, and has the potential to inform treatment. Determining whether there are generational differences in disease onset and severity is important. That information is necessary to determine whether genetics and/or environmental factors are making autoimmune diseases worse. And that information is necessary to determine how to improve genetic and/or environmental factors that affect disease onset and severity. I want to know whether there are any other studies out there on Type 1 diabetes, Autoimmune thyroid disease or Celiac disease that either confirm or refute these intergenerational differences between age of onset and severity. If this is a real phenomenon and not the result of flaws in study design or inclusion criteria, it’s crucial to know what environmental and/or genetic factors could be contributing to it.
Study Type
This study included a number of flaws, from the inaccurate characterization of participants as having Multiple autoimmune syndrome when the study chart shows many had polyautoimmunity, to conflicting numbers of participants with family members with autoimmune disease (the chart shows 20, the text vacillates between 16 and 20), to the absence of a description of intergenerational relationships. Due to these flaws, the findings of this study are interesting, but questionable.
For reference, I have ranked medical study types in order of least likely to be affected by hidden bias to most likely to be affected. Those studies that are most likely to be affected by hidden bias should be taken seriously, but not given the same weight as studies that are less likely to be affected by hidden bias. This study’s type appears in bold below.
Clinical Trial
Observational Study
Prospective
Retrospective
Cross-sectional
References
Giardino G, Aloj G, Cirillo E, Capalbo D, Maio F, Salerno M, Franzese A, Pignata C. Intergenerational anticipation of disease onset in people with multiple autoimmune syndrome. Diabetes Res Clin Pract. 2011 Nov;94(2):e37-9. doi: 10.1016/j.diabres.2011.07.022. Epub 2011 Aug 17. PMID: 21852013.